Karyopharm Stock NASDAQ: KPTI

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KARYOPHARM THERAPEUTICS (KPTI) RESEARCH NOTES


  • Commercial-stage, global pharmaceutical company with multiple FDA approvals for various oncology indications and multiple additional drug candidates in clinical development.

  • On top of Barclay's list as potential acquisition target at about $60/share.

  • Several analysts predict blockbuster sales.

  • About 90% institutional interest; average analyst target $30.

  • Industry leader in targeting nuclear export dysregulation as a mechanism to treat cancer.

  • XPOVIO® (selinexor) received first accelerated approval from the FDA in July 2019 (penta-refractory multiple myeloma).

  • In December 2020, XPOVIO received expanded FDA approval in patients with multiple myeloma as early as first relapse.

  • Xpovio is, now the only drug approved by FDA for use in both multiple myeloma and diffuse large B-cell lymphoma, discovered and developed by Karyopharm.

  • Latest corporate presentation

  • Publications and Medical Presentations

  • $230M cash, no need for cash till end of 2022 (as of 3 May 2021)

  • 2021Q1 presentation

I agree with analyst consensus that KPTI stock is in for at least a double from this point to $30+. I am also very optimistic that a buyout will happen (it's a very good option for Karyopharm).

Read this today: "Sometimes before a merger, Wall Street will crush a stock to shake out the ordinary investors. Their goal is to own as many shares as possible. If you own this stock, Wall Street can’t own it."

19 Jun 2021 - Upcoming Discussion With CEO, etc.

One of our good friends will be having a call with the CEO soon. He's a seasoned biotech investor and knows KPTI's sector well. He noted:

  • "He [Richard Paulson] left a damn good job at Ipsen for KPTI". Indeed.

Also: "I was impressed with the eltanexor news."

He wrote: "You are my inspiration!" :-) Several "passive investors" have become "active investors" when they see it in action... It makes a difference to at least remind a public company's management about their priorities.


Another seasoned investor who works in oncology wrote:

  • "Great progress in KPTI land! Looks like the new CEO is making some good changes! May be time to get back in...". He had sold his stock due to disappointment with Michael Kauffman's leadership.

First investor wrote back in May (just catching up with my notes):

  • "This is huge because they (Morgan Stanley) have access to April script data. Also, if they are projecting annual 2021 revenue of $162M, after a lousy $21.7M first quarter, that’s some significant increases to come!"

18 Jun 2021 Antengene Provides an Update on Its Latest Developments

https://www.antengene.com/news/1496.html

With the expected approvals for selinexor across multiple APAC markets towards the end of 2021, Antengene has continued to build up its experienced commercial team across China and the APAC region with plans to grow its commercial organization to up to 200 full time employees in functions including in-house marketing, field force, pricing and market access by the end of 2021.


Selinexor

Selinexor is a first-in-class, only-in-class orally available XPO1 inhibitor being developed for the treatment of hematologic malignancies and solid tumors.

  • Data from the MARCH trial of selinexor published at ASCO annual meeting in June 2021 include an objective response rate (ORR) of 26.7% in all analyzed patients with relapsed or refractory multiple myeloma (RRMM) and an ORR of 33.3% in patients with triple-class-exposed RRMM. These data are consistent with that observed in the STORM trial, from which, data had supported the accelerated approval of selinexor by the U.S. Food and Drug Administration (FDA). In addition, the data also showed an ORR of 44.4% in patients who had received prior CAR-T therapies.

  • Antengene has submitted a new drug application (NDA) for selinexor to the National Medical Products Administration (NMPA) in January 2021 with priority review granted to the NDA in February 2021.

  • Multiple combination regimens of selinexor have already included in the 2021 Chinese Society of Clinical Oncology (CSCO) Guidelines.

  • Antengene submitted NDAs for selinexor in Australia, Korea, Singapore and Hong Kong, and plans to submit an NDA for three indications in hematologic malignancies in Taiwan in Q3 2021.

  • Antengene is exploring additional indications of selinexor through two global Phase III registrational trials for the treatment of relapsed or refractory diffuse large B-cell lymphoma (RRDLBCL, the XPORT-DLBCL-030 trial) and endometrial cancer (the SIENDO trial); two registrational trials for the treatment of RRDLBCL (the SEARCH trial) and RRMM (the BENCH trial) in China; and China-only trials including for the treatment of relapsed or refractory T-cell and NK/T-cell lymphoma (the TOUCH trial).


15, 19 Jun 2021 - OpEx Week

2724 call contracts (272400 share equivalent) at $10 strike are in play this Friday. The option writers have to work really hard to get the stock to close at $9.99 or below to make those options go worthless. If they don't succeed, people who bought those options want their shares at $10 so sellers of the calls have to come up with shares (buy in open market unless they're hedged which most probably aren't since serious investors who know the stock wouldn't sell $10 calls when this price range is clearly very manipulated and grossly undervalued). So we could see fireworks on Friday, and even challenge sellers of the 1790 $12.50 call options.

~~~

Nice end of a volatile week for Karyopharm. The stock closed up, which was a wonder given biotech indices as well as other indices were all in negative territory. Probaby due to the dynamics discussed above.



10 Jun 2021 - Stock is on a tear

It's still grossly undervalued. short float down 1.7% from 21.95% to 20.25%. Shorts have a lot more shares to cover. Fake supply turning to real demand = boost in the price. New CEO means business.


9 Jun 2021 - LARGE INVESTOR HOLDING KPTI FOR $50/share

A friend of mine who owns millions in KPTI shares wrote to me yesterday:

  • "Well I'm not holding this stock thinking it's a under $50.00 investment :)"

  • (7 June 2021) In a report released today, Edward White from H.C. Wainwright maintained a Buy rating on Karyopharm Therapeutics, with a price target of $49.00.

    1. How could this one may ask, when the stock is 9.40? 9.40 to 49 is not unheard of in biotech. Even ten-baggers happen. I've seen them, and was invested in a stock that was in $2's, analysts had $12 target. Company was bought for $17 -- an 8-bagger.

    2. KPTI's solid tumor data in Q4 this year can be a game changer. That's not even priced-in in most analyst models. And the company has a lot going beside that. And I believe just correcting past management mistakes, as Richard Paulson has started to do, could freak the shorts (22% of float) and fake supply will turn into real demand, a double positive effect for the share price.

9 June 2021 - Karyopharm Announces XPOVIO® (selinexor) Data to be Presented at the European Hematology Association 2021 Virtual Congress

NEWTON, Mass., June 9, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that nine abstracts have been selected for virtual presentation, including one oral presentation, at the upcoming European Hematology Association (EHA) 2021 Virtual Congress taking place June 9-17, 2021.

To view this release online and get more information about Investor Center | Karyopharm Therapeutics visit: https://investors.karyopharm.com/2021-06-09-Karyopharm-Announces-XPOVIO-R-selinexor-Data-to-be-Presented-at-the-European-Hematology-Association-2021-Virtual-Congress


Karyopharm Announces Key Changes to Its Commercial Leadership Team

− Sohanya Cheng, Formerly of Amgen and Arrowhead Pharmaceuticals, Appointed as Head of Sales and Commercial Operations -

− Payman Darouian, Formerly of Novartis, Bristol Myers Squibb, and Sanofi, to Lead Marketing for XPOVIO® -

I hope this trend continues...

The new CEO is rocking out. He fired the CCO (John Demaree) and the SVP of Sales (Perry Monaco), and put some top-notch people in those roles instead. I hope the house cleaning will continue. The last CEO, though a medical genius, was a weak manager. Great quote about Steve Jobs explains the situation perfectly:

"My theory is that A players hire people even better than themselves. It’s clear, though, that B players hire C players so they can feel superior to them, and C players hire D players. If you start hiring B players, expect what Steve [Jobs] called ‘the bozo explosion’ to happen in your organization."- Guy Kawasaki, Chief Evangelist, Apple

8 June 2021 -- Antengene's Partner Karyopharm Therapeutics Announces Updated Data of Eltanexor in Patients with Hypomethylating Agent Refractory MDS

VERY GOOD NEWS

Jun 08, 2021, 20:00 ET

--Of the 15 patients evaluable for efficacy, 7 (47%) had mCR and 5 (33%) had SD for a total disease control rate of 80%--

--Patients with mCR had longer mOS than patients without mCR or with PD--


7 Jun 2021 - HCW Reiterates Buy with $49 Price Target

(7 June 2021) In a report released today, Edward White from H.C. Wainwright maintained a Buy rating on Karyopharm Therapeutics, with a price target of $49.00.


4 Jun 2021 - All Analysts are Bullish. JP Morgan:

JPMorgan, when price was 9.34 last month: "We are rated Overweight on KPTI shares. Following recent approval of the BOSTON label expansion in earlier-line MM and a positive CHMP opinion in the penta-refractory setting, we see blockbuster commercial potential for Xpovio based on survey feedback from USoncologists. Further, we see further optionality in DLBCL and other solid tumor indications, all under-reflected by current share levels."

4 Jun 2021 - Study Completes This Month

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB100 Administered Orally to Adults With Amyotrophic Lateral Sclerosis

3 Jun 2021 - VALUATION

"JP Morgan called Constellation Pharma extremely well, and stuck with their high PT even when the stock was nudging below the $20 level.

Yesterday they noted that the CNST acquisition came "as somewhat of a surprise, as it is a little outside of sweet spot for biotech M&A, as reflected by recent deals (i.e., companies with at least de-risked phase 3 data in hand).

Lot's of similarities with KPTI here. JPM's PT is $21, and KPTI is generally more de-risked."

~~~

3 Jun 2021 - Karyopharm Announces XPOVIO® (selinexor) Is Now Available in Additional Strength Tablets

-- Three New Strength Tablets Approved by the FDA: 40 mg, 50 mg and 60 mg --

-- New Tablet Strengths Provide Additional Patient Convenience and Dosing Flexibility --

NEWTON, Mass., June 3, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that three new strength tablets for XPOVIO, the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) medicine, are now commercially available. The availability of these additional strength tablets follows a U.S. Food & Drug Administration (FDA) approval on April 15, 2021. In addition to the original 20 mg strength tablets, XPOVIO is now available in 40 mg, 50 mg, and 60 mg strength tablets. XPOVIO tablets are available in seven different package sizes to help healthcare providers individualize the dosing and administration of XPOVIO based on patient needs. The additional dosage strength tablets may also increase patient compliance by simplifying their treatment regimen and reducing the pill burden experienced by some patients. With the introduction of these new tablet strengths and additional package sizes, there is no change to the efficacy and safety profile of XPOVIO.

2 JUN 2021

PROJECTED BUYOUT PRICE BASED ON CONSTELLATION PHARMA'S NEWS TODAY

MorphoSys to buy Constellation Pharma for 1.7B which is 8 times 2024 revenue. KPTI is trading at 1.3x so 8x would be $56/share for KPTI which is in the ball park of Barclays' $60/share buyout price target. Current price: $9.02


Karyopharm CEO Spoke at Jefferies today. Excellent talk. Here's the replay:

https://wsw.com/webcast/jeff174/kpti/1866024


Karyopharm Receives Conditional Marketing Authorization in the United Kingdom (UK) for NEXPOVIO® (selinexor) in Combination with Dexamethasone for the Treatment of Adult Patients with Relapsed and or Refractory Multiple Myeloma

-- NEXPOVIO is the First and Only Nuclear Export Inhibitor Authorized in the UK --

NEWTON, Mass., June 2, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that on May 26, 2021 the UK's Medicines & Healthcare Products Regulatory Agency (MHRA) granted conditional marketing authorization for NEXPOVIO® (selinexor), the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) medicine, in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.

Conditional marketing authorization is supported by data from the positive Phase 2b STORM study, which evaluated selinexor in adult patients with heavily pretreated, triple class refractory multiple myeloma and was published in the New England Journal of Medicine (Chari, et al.) in August 2019. Under the provisions of conditional approval by the MHRA, continued authorization for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial and is subject to additional monitoring. This marketing authorization follows a similar authorization granted by the European Commission and valid in all 27 European Union (EU) member countries which was announced on March 29, 2021.


JP Morgan: "We see blockbuster commercial potential for Xpovio based on survey feedback from US oncologists."

28 MAY 2021 - Analysts expecting at least a double from here.

Karyopharm Therapeutics (NASDAQ:KPTI)‘s stock had its “buy” rating restated by stock analysts at Robert W. Baird in a report released on Thursday,

~~~



24 MAY 2021 - Old Wall Street Trick

Wall Street manipulators' old trick: bring the price down to a ridiculously low level, and fight hard to cap it there, to make weak investors think that's the fair price; and will keep the price there to see how many people will sell. When sellers run out, the price is bid up. That's where KPTI is now, imho, ridiculously low manipulated price. Therefore, I am *not* selling in mid-9's or even several dollars higher.


23 MAY 2021 - New Patent

Karyopharm got a new patent (first item on the list below followed by other recently patents).

substituted benzofuranyl and benzoxazolyl compounds and uses thereof

multicyclic compounds and uses thereof

hydrazide containing nuclear transport modulators and uses thereof

nuclear transport modulators and uses thereof

polymorphs of selinexor

nuclear transport modulators and uses thereof

substituted benzofuranyl and benzoxazolyl compounds and uses thereof

(s,e)-3-(6-aminopyridin-3-yl)-n-((5-(4-(3-fluoro-3-methylpyrrolidine-1-carbonyl)phenyl-7-(4-fluorophenyl)benzofuran-2-yl)methyl)acrylamide for the treatment of cancer

methods of promoting wound healing using crm1 inhibitors

hydrazide containing nuclear transport modulators and uses thereof

multicyclic compounds and methods of using same

substituted 2,3-dihydrobenzofuranyl compounds and uses thereof

nuclear transport modulators and uses thereof

substituted benzofuranyl and benzoxazolyl compounds and uses thereof


20 MAY 2021 - Lot of Goodies

Tomorrow, 21 May is Annual Shareholder Meeting. Should be interesting to hear the new CEO speak from position of being fully in charge.

ASCO coming up in 2 weeks. The hedge fund short cartel who's been promoting distortions and disinformation about Karyopharm via their puppet doctors, is in for an unpleasant surprise at ASCO.

  • Sixteen abstracts have been selected for virtual presentation, including one oral presentation, at the upcoming 2021 American Society of Clinical Oncology (ASCO) Annual Meeting taking place June 4-8, 2021.

I think it's fair to assume we'll have fireworks by ASCO. That's only 2 weeks away.

An astute shareholder friend wrote:

Interested to see RAS-mutant related study notes from abstracts today. Abstract 2 - "the data suggest that selinexor-containing regimens could be active in other RAS-mutant cancers" Abstract 8 - "Greater anti-tumor activity was observed in patients with RAS mutations despite the absence of high microsatellite instability and/or deficient in mismatch repair"


New data show pain worsened faster, and more dramatically, in patients given placebo versus selinexor for dedifferentiated liposarcoma, as measured by the European Organisation for Research and Treatment of Cancer’s 30-item core quality of life questionnaire.

Patients with advanced dedifferentiated liposarcoma (DDLPS) had less pain and slower worsening of pain when treated with selinexor (Xpovio) compared with placebo, according to new data from the phase 3 portion of the Selinexor in Advanced Liposarcoma (SEAL) trial (NCT02606461).1



14 May 2021 - Big News Out of KPTI's Chinese Partner

Antengene Announces the Completion of Its Manufacturing Center in Shaoxing to Accelerate the Commercialization of Novel Anti-Cancer Therapies

"At this site, Antengene plans to soon initiate the manufacturing of selinexor, the company's first selective inhibitor of nuclear compound."

"At this new facility, we will begin the commercial manufacturing of selinexor in China to meet the future demands from patients.""

"efficiently supply high quality drugs to patients in APAC."

"As a novel therapy targeting a broad spectrum of tumor types, selinexor has demonstrated antitumor activity in multiple hematologic malignancies and solid tumors, and is already approved in the U.S. for the treatment of multiple myeloma and diffuse large B-cell lymphoma. Antengene has submitted new drug applications (NDAs) for selinexor in China and multiple APAC markets, and expects to receive market authorizations during Q4 2021 and Q1 2022."


13 May 2021

Move your shares from Type2(margin) to Type1(cash). Call your broker and ask for the shares to be journaled to Cash - or open Type Cash account and move the shares there. This ties up shorts' hands.


Today I moved (journaled) a bunch of shares shares from margin account (type 2) to cash account (type 1). When in margin your shares are often lent out without you knowing. Or the shares don't even exist. You just have a marker in your account; phantom shares. But if you journal it to type Cash, the shares are recalled and shorts get the email they don't want to see: deliver!


Options

  • Someone bought 7100 shares equivalent of January 2022 $20 calls betting the price will be over $20.60 by January.

  • Someone bought 21400 shares equivalent of June 2022 $10 calls betting the price will be over $10.45 by June OpEX.


Karyopharm/Antengene's selinexor application OK'd in China for endometrial cancer

China's National Medical Products Administration (NMPA) has approved the Investigational New Drug (IND) application for a Phase III trial to evaluate the safety and efficacy of selinexor (Xpovio) being co-developed by Karyopharm Therapeutics (KPTI) in the treatment of advanced or recurrent endometrial cancer (the SIENDO trial).

Antengene is currently conducting five late-stage clinical trials of selinexor for the treatment of MM, DLBCL, non-small cell lung cancer, and peripheral T and NK/T-cell lymphoma.

Antengene has submitted NDAs for selinexor in multiple Asia Pacific markets and was granted the Priority Review status by China's NMPA and an Orphan Drug Designation by the Ministry of Food and Drug Safety of South Korea.


May 2021


Antengene

Antengene Announces Selinexor Added to Multiple Treatment Regimens in 2021 CSCO Guidelines



12 May 2021


SELINEXOR DATA


Selinexor data will be reported in 12 presentation at EHA meeting in June. One presentation is particularly interesting, "EFFECTS OF SELINEXOR ON PREVIOUSLY TREATED MULTIPLE MYELOMA (MM) WITH RAS-MUTATIONS"


Conclusion. Despite typically having the worst outcomes, pts with RASmut MM had a similar benefit from XVd as RASWT MM, showing that the XVd combination can overcome traditionally poor prognostic RASmut. Mechanistically, selinexor induced down regulation of GCK and enhanced killing of RASmut MM cells. With a manageable safety profile, the XVd regimen could provide a viable treatment option to improve PFS and OS in pts with MM with RAS mutations.


NOTES FROM EARNINGS CALL

https://investors.karyopharm.com/download/KPTI+Q1+2021+Earnings+Presentation.pdf

  • XPOVIO prescription (RX) demand increased 17% in Q1 2021 as compared to Q4 2020 following expanded FDA indication granted in December 2020

  • Over 160 new physicians / accounts prescribed XPOVIO for the 1sttime in Q1 2021

  • Ended Q1 2021 with $233.6M in cash, cash equivalents, restricted cash and investments

  • 16 abstracts selected for presentation at 2021American Society of Clinical Oncology (ASCO) Annual Meeting (June 2021)

  • Potential partners have also expressed a very strong interest in our solid tumor pipeline.

  • "As we're in the process of discussing and evaluating potential partners in Europe and Japan, with the recent marketing authorization, the EU, as well as the acceptance of the EMA for BOSTON indication, which is where we know much of our value to us, and potential partners will be generated, we need to continue to explore those partnership opportunities. And the immediate priority is around ensuring we bring XPOVIO to the EU and multi myeloma. However, potential partners have also expressed very high interest in our solid tumor pipeline." CEO Richard Paulson

11 May 2021

Drs. Shacham and Kauffman took a big salary cut and their stock options were forfeited

I respect Drs. Kauffman and Shacham deeply and have had zoom calls with both. Very genuine people. I'm not impressed with their management of Karyopharm but scientifically they're geniuses.

I have been concerned that change of guards might be symbolic and the status quo / founder's syndrome may go on but these filings tell me this change is fundamental, and I much welcome it. Good job Board of Directors.

https://www.sec.gov/Archives/edgar/data/1503802/000119312521146624/d172053dex103.htm

https://www.sec.gov/Archives/edgar/data/0001503802/000119312521146624/d172053dex102.htm

Furthermore, as of end of the year, Dr. Shacham will no longer be the Chief Scientific Officer.

From KPTI Investor With 250,000 Shares

A friend who owns 250,000 shares of KPTI wrote me today:

"I didn't invest for a $20 or $30 buyout! I invested thinking $50 minimum. I'm genuinely feeling good about the company now."

KPTI insiders are buying in open market

Great sign. Two insiders reported today and yesterday of open market buys. Today report came that KPTI's Chief Medical Officer Jatin Shah just bought over 23,000 shares at around 8.60 for sum of $200,000. What an endorsement from someone in the know.

Yesterday one of the Board members bought in the open market.

Selinexor, Bortezomib, and Dexamethasone Combination Proves Effective for Myeloma

Somebody tell those bashers like Aaron Goodman and Vinay Prasad who have apparently had conflict of interest, to read this and weep: Fact is Selinexor is a great, life-saving drug:

https://www.onclive.com/view/selinexor-bortezomib-and-dexamethasone-combination-proves-effective-for-myelom

“The BOSTON study is the first study to assess the efficacy of once-weekly selinexor as part of a triplet therapy in patients with multiple myeloma who have had 1 to 3 prior therapies,” said Joseph Mikhael, MD, in an interview with OncologyLive®. Mikhael is a professor in the Applied Cancer Research and Drug Discovery Division of the Translational Genomics Research Institute (TGen), an affiliate of City of Hope Cancer Center in Phoenix, Arizona

“The combination of selinexor and dexamethasone and bortezomib demonstrates synergistic cytotoxic effects in multiple myeloma in vitro, and increased antitumor activity in murine xenograft multiple myeloma models in vivo, including those resistant to proteosome inhibitors,” Mikhael explained.

“In the primary end point data, we can see that the SVd group demonstrated a sustained progression-free survival advantage over the twice-weekly Vd group with a 30% reduced risk of progression or death,” Mikhael said.

“Further, there was a consistent PFS benefit with SVd across multiple patient subgroups,” Mikhael added. “The risk of progression or death was noticeably lower in all subgroups including patients [aged] 65 years and older, those with high-risk cytogenetic abnormalities, and patients who received 1 prior line of therapy.”

“Patients in the SVd group also experienced significantly higher rates of deep responses than the Vd arm with 16.9% of patients experiencing a [CR plus sCR] and 44.6% of patients experiencing a VGPR [or better] as compared with 10.6% and 32.4% for CR [plus sCR] and VGPR [or better], respectively in the Vd group,” Mikhael said.1

“The median time to response was shorter in patients who were given SVd, [and] The duration of response was longer in the SVd arm,” Mikhael added. The median time to response was 1.4 months in the SVd arm and 1.6 months in the Vd arm; the median duration of response was 20.3 months and 12.9 months, respectively.

“Collectively, these findings suggest that SVd provides significantly higher PFS, overall response, and duration of response than Vd. Patients also experienced deeper and faster response than those not given selinexor,” Mikhael said.

9 May 2021 - Musings on New CEO, Buyout, Stock Action

Someone wrote: "I feel confident in the new CEO and the pipeline of products. A question in the back of my mind... What are the odds of being in a new CEO as part of an a coming merger? KPTI has the medications and the science and merger with a sister company or a sales team agreement could change it all."

The CEO has ties to several potential suitors. He has deep experience / relationships with the following companies:

§ He was the CEO of Ipsen North America, a global biopharmaceutical company focused on innovation and specialty care in areas of oncology, neuroscience and rare diseases. Ispen would be a good suitors. They have been expanding, and Karyopharm is a good strategic fit for them.

§ He was at Amgen for 10 years holding varying leadership positions across Europe and North America, including Vice President and General Manager of Amgen’s U.S. Oncology Business Unit, and prior to that served as the Vice President of Marketing for Amgen’s U.S. Oncology Business, General Manager of Amgen Germany, and General Manager of Amgen Central & Eastern Europe. There are several key words here that are extremely important to Karyopharm: Oncology, Marketing, and his deep experience in Europe is icing on the cake given Karyopharm recently obtained European approval and will likely get a second approval in a matter of months.

§ He held a number of global leadership positions at Pfizer Inc., including serving as General Manager of Pfizer South Africa and Pfizer Czech Republic.

§ He held a variety of sales, marketing, and market access roles at GlaxoWellcome in Canada. Again, full of key buzz words relevant to Karyopharm.

Any of these companies could buy Karyopharm (and there are more). Now, whether his appointment is tied to an existing nurturing merger situation, is a mystery to me. If anyone has the answer please share it with me.

KPTI

The stock hit a new low last week to upper 7's, but rebounded nicely to mid 8's. There are 3 forces that can engaged in pressuring the price, aside from anyone who sells for personal reasons or in relation to indices.

§ Short sellers

§ Prospective buyers

§ Traders who sold and want to buy at lower price

§ Potential acquirers engaged in manipulating the shares (this is a documented fact that happens).

Except for the last one, the rest have a goal to buy the stock. The last one has the goal of just pressuring the stock. Of course it's risky business for them as manipulation is costly. I don't know the topic first hand but from a distance it seems that at some point any of these entities calls the bottom and starts buying.

And you can be sure, the regulators will be watching very soon. I have ties to FINRA and am making a massive report with documentation on the suspicious activity on the stock which FINRA will look. The last report we made, led to FINRA stopping the abusive manipulation (I had a couple of conference calls with them to help them out, following the report I and my friends wrote) - click here to see it.

A lot also depends on the company's execution. With the new CEO in charge I am relaxed about the company (I was nervous before due to founder's syndrome at the company). I just hope he's not a symbolic CEO and the founders are not pulling the strings from the background. Two big letters are being prepared by investors to the company.

Also IR has a key role. Some old-timers are not happy with Karyopharm's IR efforts, social media presence, etc. -- and there's evidence of ineffective handling in some of these areas. That's another area the new CEO to put under microscope.

6 May 2021 - Catalysts, Turnarond, Buyout Prospects

I'm excited about the rest of the year. There are a number of key catalysts coming up that can turn the KPTI universe around (for the better). Add to that a new CEO who has all the right relationships with big pharma. Just as the long-term shareholders who follow and know the company well have told me, I expect competitive bidding after solid tumor data later this year and the company getting bought out for a luscious premium.

6 May 2021 - Short Interest Freaking About New CEO


Shorts didn't like the CEO change. They probably viewed Dr. Kauffman as an ideal CEO because of his failures and lack of track record in building shareholder value. Mr. Paulson is a big threat to the shorts: he can shake the entire short thesis/paradigm. And this entire fake game shorts are putting on, in my opinion, with manipulating the price, could be a symptom that they're freaked about Mr. Paulson. It's conceivable that shorts break ranks with each other and start covering at any time and stock could rebound.

I've never seen a biotech or any company with such strong analyst endorsement be in a hole that Karyopharm is in (which is a result of mismanagement in my opinion). The science is not in hands of a competent CEO who's got everything it takes to make Karyopharm a success.

A large investor from the industry was telling me recently, when we were formulating the letter to the board, the kinds of qualities the new CEO must have. Mr. Paulson fits all of that.

6 May 2021 - Note on Manipulation

Tough day. I've been through a few of these before. Yes shorts can manipulate a stock. They're experts in managing (and ruining) investor psychology. They use all kinds of tactics with the stock and options to send weakness signal, to prompt people to sell so they can cover.

Another current here at play is potential acquirers who can engage in manipulating the stock so they can buy a company at a lower price. This is a well documented fact from industry insiders.

The key is whether the company's product/story has merit or not. Shorts succeed in ruining companies with a fluff product/story. KPTI's offering is absolutely solid. So in this case, shorts would want to cover. But they use index weakness, and events to manipulate the stock. It's their chance to drill into investor psychology. At some point strong hands remain, and shorts stop taking on additional risk. Manipulation is costly. Past mismanagement is the main culprit. But we have a new CEO. I'm very optimistic.

5 May 2021 - Advice from Billionaire Charlie Munger

"If you can’t stomach 50% declines in your investment, you will get the mediocre returns you deserve."

5 May 2021 - report to FINRA on manipulation of stock & options

Shorts are playing a dirty game that's probably unlawful. There are several clues to the shenanigans. I'll be filing with my contacts at FINRA shortly to investigate it. Last time we put a stop to abusive treatment of a stock.

5 May 2021 - New CEO is fully loaded

Richard Paulson is a beneficiary owner of 559,800 shares

4 May 2021 - Important Comments

§ During the first quarter of 2021, XPOVIO generated net product sales of $21.7 million, representing a 7% increase as compared to the fourth quarter of 2020 and a 35% increase as compared to the first quarter of 2020. Net sales for the first quarter of 2021 were largely driven by prescription demand from both academic and community-based oncologists for patients with multiple myeloma. Approximately 1,170 XPOVIO prescriptions were filled in the first quarter of 2021 as compared to approximately 1,000 prescriptions in the fourth quarter of 2020, representing a 17% increase in patient demand from the prior quarter. Further, over 160 new physician prescribing accounts were added in the first quarter of 2021, which included physicians treating both myeloma and diffuse large B-cell lymphoma (DLBCL). Additionally, prescription demand in the first quarter of 2021 was the highest generated since XPOVIO's initial accelerated FDA approval in July 2019.

§ Morgan Stanley reiterates Overweight opinion and $32 PT, citing the importance of prescription data trends over reported sales. "Prescription volumes for Xpovio increased 17% from 4Q20, with the recent approval of the BOSTON regimen being the primary contributor to the incremental growth. We continue to expect the drug to gain momentum and ramp sharply as the year progresses, with inclusion of the BOSTON data on the label."

§ New CEO is key. He worked at IPSEN on launch of EXEL's Cabometryx and knows EU mkt well.

§ ASCO June 4-8. Karyopharm will be there. Found abstract titles with Selinexor for 16 presentations at ASCO meeting next month. It shows a lot of interest to this drug from many investigators.

§ Weekly dosing is the norm and the combo with Kyprolis will add to its uptake in the Myeloma arena. Endometrial by next year and most likely Europe this year. Be patient and be an investor not a trader with this one. I would be surprised if we do not see 20s in the next 12 to 18 months. May not be what some want to hear but that is still a huge return. (Dollar cost average in on this one.) I know some thought this was going to $49. Sorry Baird but I would be surprised...... Best of luck team!

4 May 2021 - Good article: Karyopharm taps Amgen, Pfizer veteran as CEO

https://www.bizjournals.com/boston/news/2021/05/03/karyopharm-taps-amgen-pfizer-veteran-as-ceo.html

4 May 2021 - Tough day for KPTI and the markets but Karyo's story is solid.

Some of the most rewarding stocks I’ve owned put investors thought Chinese water torture before the big reward. Wall Street always wants to live and if retail holds shares and Wall Street is short shares, WS assumes it’s retail that has to provide the shares at the price WS wants. So, they grind the nerves of Main Street and they often succeed in getting Main Street to throw in the towel.

Today’s painful, exaggerated drop in KPTI is influenced by the same motive. The tough investors I knew who kept their shares through the tough times ended up doing real well as long as the company’s story is solid, and Karyopharm’s is a rock solid story. Just my 2- cents.

3 May 2021 - Morgan Stanley reiterated Overweight & $32 price target on KPTI.

Morgan Stanley updated KPTI minutes ago, MAINTAINING their Overweight rating and $32 PT. From the report: "While it is too early to determine the long term trajectory of Xpovio post the BOSTON approval, script data suggests that volumes are starting to inflect. This could bode well for the second half. We expect revenue will grow sharply as the year progresses as 1) the increased growth from the BOSTON regimen adds new patients and 2) the higher duration of therapy for this regimen will keep patients on drug for considerably longer. We remain above consensus on 2021 Xpovio sales ($162M vs. 146M), predicated on continued volume growth and stabilization of net price in 2Q21 and beyond."

3 May 2021 - Large Retail Holders

There are several large retail shareholders I know. One of them whom I know and trust, wrote to me today that he's upped his holding to 250,000 shares and is planning to hold. We're all happy with having a new CEO. I assume institutions have a similar sentiment.

3 May 2021 - Ipsen Pharma & Karyopharm -- & Pfizer

An insider said a few weeks ago (I heard today) that the Board has been very active (more active than he's ever seen in any other company) -- which is a very good thing -- and he won't be surprised if Ipsen Pharmaceuticals buys them because they want to grow their oncology business...and US footprint.

A few weeks later Richard Paulson became our new CEO. Mr. Paulson comes from Ipsen!! He was the CEO of Ipsen North America.

Ipsen buying Karyopham would be a good fit. I don't think they have the kind of money Drs. Kauffman and Shacham would like to get for the company. I'd guess Ipsen could offer 2 billion (which is around $26/ share). I'd be very happy with that.

A thoughtful friend and long term KPTI investor wrote to me today in response to that idea:


"Interesting, I screened Ipsen before after reading MK statements that they’d go with a mid cap (<$10B) or smaller European partner. Last paragraph- https://pharmaboardroom.com/articles/us-biotech-commercialisation-strategies-how-karyopharm-ionis-are-approaching-us-vs-row/

And on the Feb call they mentioned they expect to announce the partner in the next few months."

~~~

PS -- Mr. Paulson also has deep ties to Pfizer. Rumor on weekend for PFE takeover of KPTI. Let's see...

3 May 2021 - NEW CEO / PRESIDENT -- !!!YES!!!

HALLELUJAH - PRAISE THE LORD - WE HAVE A NEW CEO/PRESIDENT. WATCH OUT SHORTS. YOU'RE FUCKED.

Time To Celebrate!! Congrats in particular to Drs. Michael Kauffman and Sharon Shacham for stepping down as CEO/President. A big overhang for the company and the stock is removed. Most founders don't have the insight and character of Drs. MK & SS to let go of leadership when it's time.

https://investors.karyopharm.com/2021-05-03-Karyopharm-Announces-the-Appointment-of-Richard-Paulson-as-President-and-Chief-Executive-Officer

Karyopharm Announces the Appointment of Richard Paulson as President and Chief Executive Officer

-- Richard Paulson, Recent Chief Executive Officer of Ipsen North America and Former Vice President and General Manager of Oncology at Amgen, Brings Wealth of Commercial Leadership and Global Strategic Experience --

-- Michael G. Kauffman to Remain on Board of Directors and Assume New Role as Senior Clinical Advisor--

Exactly the background you want for this role:

Richard Paulson

President and Chief Executive Officer

Mr. Paulson was appointed President and Chief Executive Officer of Karyopharm in May 2021 and has served as a member of Karyopharm’s Board of Directors since February 2020. He was previously an Executive Vice President of Ipsen Pharmaceuticals, Inc. and Chief Executive Officer of Ipsen North America, a global biopharmaceutical company focused on innovation and specialty care in areas of oncology, neuroscience and rare diseases, from February 2018 to May 2021. Mr. Paulson previously worked at Amgen for 10 years holding varying leadership positions across Europe and North America, including Vice President and General Manager of Amgen’s U.S. Oncology Business Unit, and prior to that served as the Vice President of Marketing for Amgen’s U.S. Oncology Business, General Manager of Amgen Germany, and General Manager of Amgen Central & Eastern Europe. Prior to Amgen, Mr. Paulson held a number of global leadership positions at Pfizer Inc., including serving as General Manager of Pfizer South Africa and Pfizer Czech Republic. Mr. Paulson also previously held a variety of sales, marketing, and market access roles with increasing seniority at GlaxoWellcome in Canada.

Mr. Paulson has an MBA from the University of Toronto, Canada and an undergraduate degree in commerce from the University of Saskatchewan, Canada.

~~~

Earnings Presentation

https://investors.karyopharm.com/download/KPTI+Q1+2021+Earnings+Presentation.pdf

3 May 2021 - Pre Earnings Report Dynamics

Earning call at 8:30 Eastern today.

Pre earning reports dynamics:



§ Excellent Life-saving medical breakthrough

§ Regulatory derisked

§ Analysts very optimistic

§ Stock very undervalued

§ Ripe buyout target

§ Pharmas already knocked on their door

§ Suddenly lots of posts with very positive predictions (strange)

Yet

§ Stock is under the shorts' thumbs (because of a weak CEO, IMO, because management matters and KPTI's CEO is a great medical doctor but has no track record in running a successful business, not education in management, and he admits he doesn't have what it takes and wants to stop down (WHEN?)



§ It should be worth at least 2B today (and bought for at least 3B) is valued at 700M b/c of management issues which can be solved overnight with the founders stepping down from CEO/President role.

Some investors have written that they're expecting the worst but are hoping for the best. If they just release bad numbers and the same dysfunctional management continues and they don't tell the public same things they told me (new CEO, not go it alone, etc.), then the stock could temporarily tank. Given the strength of the science it'll be a great buying opportunity , so I expect it'll rebound.

If they add good news like new CEO, partner..., stock will take off.

No matter what, I will hold my shares because I know, with a new competent CEO the company can get fairly valued and that's at least $22/share. I can wait.

2 May 2021 - $49 PRICE TARGET REITERATED BY ANALYST

In a report released today, Edward White from H.C. Wainwright maintained a Buy rating on Karyopharm Therapeutics (KPTI), with a price target of $49.00.

The word on The Street in general, suggests a Strong Buy analyst consensus rating for Karyopharm Therapeutics with a $29.25 average price target, representing a 184.0% upside.

In a report released yesterday, RBC Capital also reiterated a Buy rating on the stock with a $24.00 price target

Published On: Tue, 30 Mar 2021 10:15:00 GMT

Being at $9.30, a $49 price target seems unrealistic but I have personally seen analyst be right with such projections. I owned a biotech at 2.50, analysts had 7, 12, 15 targets for it that seemed so unrealistic. It was taken over at $17 and an army of shorts got crushed.

2 May 2021 - Earnings Call

3 May the company is having its quarterly earnings call. I am hoping they tell the investors what they told me -- the public deserves to know it -- that:

1) The company no longer wants to go-it-alone. CEO Dr. Michael Kauffman has said on a number of occasions that they want to go it alone. In December 2020 he said they can be the next Celgene. [by the way, when I see a Medical Doctor as a CEO that's always a red flag for me -- but in my doing due diligence on Karyopharm I missed that because I was so mesmerized by their amazing science]. They need to make it clear to Wall Street that they are open to being acquired. CEO told me they've had interested parties but they told them "not yet". But now it's time they are open to overtures. I told him blundly, with all due respect, I don't trust him with negotiating with Big Pharma (I just don't see that talent in him). He said some senior board members get engaged in such talks. We still need a strong business-minded CEO to lead such discussions.

2) The CEO wants to step down because he doesn't think (rightly so) he's fit for that role (he has no commercial experience, he has no experience building shareholder value, and prior to Karyopharm, he never had a CEO role that was successful for shareholders, and all his other experiences were medical/scientific. So clearly the wrong profile for this stage of the company's growth, and he knows it, Thank God.

But between him and his wife, Dr. Sharon Shacham who is a celebrity in biotech (they're both geniuses in my opinion and I highly respect both of them), who is serving as president and CMO, they've got the company stuck in a case of founders syndrome. They need to relinquish their CEO/President position and the stock will take off. Shorts love scientific founders who fail shareholders at CEO.

So those announcements will boost the stock.

Regarding earnings, I think the numbers will be poor because of Covid and because of management issues. Management matters, and impacts all aspects of a company's business, including dealing with currents that impact sales. This was elaborated in detail in a letter we sent to the Board. But I'm hoping other news will offset the poor sales. And I'm really hoping we don't get excuses and rationalizations because the key issue (and risk) is, as the CEO himself admitted, him being in the wrong role. And he's told the Board. So the Board has a duty to act quickly on that. Let's hear the news.

A main Issue in founder's syndrome is such nice ideas are often lipservice because deep down the founder finds excuses to continue – kind of like being addicted to smoking. Smokers always defers quitting for a future date that never comes. It's called psychological time. See my article.

1 May 2021 - Multiple myeloma triplet therapies: baseline characteristics and control groups

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00271-3/fulltext?rss=yes

26 Apr 2021 - J.P.Morgan very bullish on kpti-- it expects 125% return in next 8 months.

In a new report, J.P.Morgan reiterated their Overweight rating, with $21 price target for December 2021, citing catalysts that could change that picture, e.g., data readouts later this year. "Summary Investment Thesis and Valuation We are rated Overweight on KPTI shares. Following recent approval of the BOSTON label expansion in earlier-line MM and a positive CHMP opinion in the penta-refractory setting, we see blockbuster commercial potential for Xpovio based on survey feedback from US oncologists. Further, we see further optionality in DLBCL and other solid tumor indications, all under-reflected by current share levels."

"With the phase 3 SIENDO study ongoing and topline readout expected by year-end 2021, a 2-3 month benefit on mPFS (HR of 0.6) could be viewed as clinically meaningful. Accordingly, our model now includes risk-adjusted peak forecasts in endometrial cancer of ~$200M with50% POS."

26 Apr 2021 - NEW FILING IN EUROPE, APPROVAL EXPECTed IN 5 TO 8 MONTHS

Karyopharm Announces European Medicines Agency's Validation of its Type II Variation Marketing Authorization Application for NEXPOVIO® (selinexor) in Combination with Velcade® (bortezomib) and Dexamethasone for the Treatment of Adult Patients with Multiple Myeloma

- EMA Regulatory Decision Expected in the Fourth Quarter of 2021 -

About Multiple Myeloma in Europe

Multiple myeloma (MM) is an incurable cancer with significant morbidity and the second most common hematologic malignancy. In 2020, there were approximately 51,000 new cases and 32,000 deaths from MM in Europe1. While the treatment of MM has improved over the last 20 years, and overall survival has increased considerably, the disease remains incurable, and nearly all adult patients will eventually relapse and develop disease that is refractory to all authorized anti-MM therapies. Therefore, there continues to be a high unmet medical need for new therapies, particularly those with novel mechanisms of action.

About NEXPOVIO (selinexor)

NEXPOVIO, which is marketed as XPOVIO® in the U.S., is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) medicine. NEXPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). NEXPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. NEXPOVIO (selinexor) has been granted conditional marketing authorization by the European Commission in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.

22 Apr 2021 - NEW TRIAL WITH

Karyopharm today initiated a new clinical trial with selinexor in combination with Bristol-Myers Squibb Opdivo (nivolumab) and Yervoy (ipilimumab) for patients with advanced solid malignancies.

https://clinicaltrials.gov/ct2/show/NCT04850755

19 Apr 2021 NEW POSITIVEDATA

"The Phase 3 SEAL study suggests that selinexor has enhanced clinical activity and a manageable safety profile in patients with DDLPS, a very rare and aggressive form of cancer where there are very few treatment options available. In addition to meeting its primary endpoint with a statistically significant improvement in progression-free survival (PFS), treatment with selinexor also resulted in improvements in key quality of life parameters as compared to patients treated with placebo," said Jatin Shah, MD, Chief Medical Officer of Karyopharm. "The results highlight that the reduction in tumor growth, as measured by objective radiographic PFS, is accompanied by clinically important reductions in pain, with minimal effects on other aspects of quality of life. Since pain is one of the most devastating symptoms associated with advanced and progressing DDLPS, the significant reduction in pain, and a delay in the time to definitive deterioration reported by patients in the selinexor arm, combined with the convenience of an orally administered therapy, could represent a meaningful clinical benefit to patients."

"We are pleased to see the first set of data from the Phase 3 SEAL study now published in a peer-reviewed medical journal," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "These data continue to support our overarching development strategy to pursue additional solid tumor indications where we believe selinexor can demonstrate meaningful clinical activity both as a single agent, and more importantly, as part of future combination regimens for patients battling cancer."

https://newsfilter.io/a/938596ac731686227feedde658454a7a

18 Apr 2021 KPTI musings

~~~

A large investor wrote:

Thanks Reza. I’ve been doubling down and buying more kpti shares. I really believe in the science and hope we are all soon rewarded as shareholders. Have a good day!

~~~

KPTI is being held down by the founders who are scientific geniuses but have been a failure in building shareholder value. I've been busy (not that I've been looking for things to do) in digging into the KPTI story. It's well worth it because

§ The science is amazing, unique, and it saves lives.

§ The stock is very undervalued. Average analyst estimate is $30.

§ Short interest has been in control because of weak leadership - so a change in leadership can quickly turn the stock around.

§ Short thesis is weak, and backed by a couple of rogue doctors. We've found hot tips on this topic and are investigating it.

§ The CEO agrees he's not fit for the job - we expect a CEO change soon, like immediately hopefully.

§ I'm not expecting a strong quarter but am expecting good news, like CEO stepping down, and maybe EU partnership.

§ Rich pipeline; lots of irons in the fire.

§ Prime buyout candidate. Mismanagement has failed to build necessary relationships (e.g. sales synergies), and big pharma is probably pulling some strings against the stock to help it buy the company for cheap. The missing piece is a strong CEO who can grab this bull by the horn. I'm very confident that a strong new leader (and full, complete relinquishing of power by the miserable current leadership) can execute a sharp turnaround where the stock quickly goes to upper teens, followed by a buyout in the 30's or 40's. I know investors (and analysts) who think the buyout price should be even higher, but I will be very happy with $30 or $40. Barclay projected $60 buyout price.

~~~

You have to look at the big picture my friend.

1) Management matters - otherwise why not make the janitor as the CEO and save a ton of money.

2) Management being inept in building shareholder value makes the company prime target for shorts because they know management will fuck up shareholder value. of

3) A competent CEO can do a lot, trust me. And an incompetent one (in running a business not a charity that enriches the founders, as we've seen can ruin shareholder value. Incompetence in that area has many consequences and we've seen an whole array of consequences. A CEO competent in making a business a success can right all those wrongs.

4) Michael Kauffman realizes the problem and wants to step down. Outside forces can just help expedite the transition out of a rotten status quo.

5) Dr. Kauffman being the CEO is the single biggest risk about this investment, in our opinion.

6) Yes, weak leadership, inept in managing the market, does effect the demand channel as well when you understand the deeper currents.

7) I don't agree with your idea that MK won't be replaced until a buyout. I don't trust him negotiating a buyout, or anything for the matter.

13 APR 2021 - ANALYST REITERATES BUY WITH $24 PRICE TARGET

RBC Capital Thinks Karyopharm Therapeutics’ Stock is Going to Recover.

RBC Capital analyst Brian Abrahams maintained a Buy rating on Karyopharm Therapeutics (KPTI) on April 8 and set a price target of $24.00. The company’s shares closed last Friday at $10.02, close to its 52-week low of $9.75.

Currently, the analyst consensus on Karyopharm Therapeutics is a Strong Buy with an average price target of $30.40, representing a 201.9% upside. In a report issued on March 30, H.C. Wainwright also maintained a Buy rating on the stock with a $49.00 price target.

https://www.smarteranalyst.com/new-blurbs/rbc-capital-thinks-karyopharm-therapeutics-stock-is-going-to-recover/amp/

8 APR 2021 - American Association for Cancer Research

11 poster presentations on 10 April.

https://www.abstractsonline.com/pp8/#!/9325/presentations/Selinexor/1

§ 1049. Optimizing the treatment schedule of selinexor in combination with decitabine in AML

§ 1058. Inhibition of nuclear transport protein XPO1 potentiates the effect of KRAS G12C inhibitors

§ 1061. Characterization of synergistic selinexor combinations with dexamethasone, pomalidomide, elotuzumab, and daratumumab in primary MM cells

§ 1091. Nuclear export inhibitor KPT-8602 synergize with PARP inhibitors in castration resistant metastatic prostate cancer

§ 1228. Novel small molecule inhibitors that target the exportin binding pocket of TOP2A for the treatment of multiple myeloma

§ 1341. Inhibiting the nuclear exporter XPO1 and the antiapoptotic factor BCL2 is synergistic in XPO1 and SF3B1 mutant hematologic malignancies

§ 1380. Synergistic effect of the combination of XPO1 and mTORC1/2 inhibition for the treatment of triple-hit DLBCL

§ 2383. Mir-7974: An oncogenic miRNA that perpetuates gastric cancer

§ 3040. Inhibition of Exportin-1 as part of combinatorial treatment for patients with high-risk neuroblastoma

§ 738. Targeting metabolic vulnerabilities of endocrine resistant breast cancers using XPO1 and NAMPT inhibition

§ 994. Investigating inhibition of nuclear export in breast cancer cells

7 APR 2021 - LookiNG BEYOND Q1 RESULTS

I think we should assume Q1 numbers will suck due to Covid and management issues. In my talks with the President and CEO they both reiterated how great the drug is, and I believe it. A couple of doctors are bashing the drug but they're probably also consulting for hedge funds :-). The drug saves lives!

I'm looking beyond Q1. To change of leadership which MK told me is coming because he knows his limitations and he believes they need a CEO with a different skillset than being a good doctor.

New CEO announcement will rattle the shorts who are counting on the founder's syndrome that's bogged the company down, and it's not just about lack of commercial skills.

Rich pipeline. Looking forward to more positive data. MK also said they are now open to selling the company - that there were suiters in the past but they told them "not yet" but now is the time. Let the competitive bidding begin. I think Karyopharm will be bought within the next 12 months. And I'm willing to wait.

6 APR 2021 - News & analysts

Antengene Announces NMPA Approval of IND Application for ATG-019 in Patients with Advanced Solid Tumors or Non-Hodgkin's Lymphoma... ATG-019 is a global first-in-class oral dual PAK4/NAMPT inhibitor developed by Karyopharm Therapeutics Inc. (NASDAQ: KPTI). Antengene reached an exclusive agreement of cooperation and authorization with Karyopharm and obtained the exclusive development and commercialization rights of ATG-019 in multiple Asia-Pacific markets, including Greater China, South Korea, Australia, New Zealand and ASEAN countries.

~~~

4 APR 2021 - URGENT NEED FOR NEW CEO; current ceo agrees change is needed

https://pharmaboardroom.com/interviews/michael-g-kauffman-founder-ceo-karyopharm-therapeutics/

Last line: "As a company, Karyopharm has great drugs and great technology with really no competition at the moment so we truly have the potential to become the next Celgene."

That was in 2020. A very delusional statement of a CEO who has no background business/commercial world and no education in it either. A great doctor/scientist. Karyopharm urgently needs a new CEO. Like yesterday!

He said the same thing in 2014: we will go it alone. Recently he told me he no longer sees that as a good option and thinks the company will be better off if it's sold. Suiters had come before, company said not yet. But now they're talking again, IMO, based on what I read between the lines. That the board is involved in it. But I told him I don't trust you negotiating a deal, as much as I like you as a man of integrity and a great doctor/scientist.

He also said he agrees with me and sees his shortcomings and has told the Board. But that means it could take months due to inertia of status quo, while urgent action is needed, which may mean an interim CEO.

Amazing science in hands of a top notch well-qualified businessman/salesman/commercial-guru CEO will make KPTI value go to the moon. This is the opinion of several investors in KPTI who hold a significant number of shares. And Dr. Kauffman seems to agree. But where's action?!

2 APR 2021 Letter to board

Appendix 3 (Final Addendum) went to the Board citing intelligence from a Big Pharma, and other tips.

1 APR 2021 KPTI MAILING

Hi Folks

KPTI got European approval.

§ NEXPOVIO is the First and Only Nuclear Export Inhibitor Authorized by the European Commission

§ Second European Regulatory Filing Based on Phase 3 BOSTON Data Expected by April 2021

The stock is heavily manipulated by shorts because of founder's syndrome, IMO. But analysts continue to be very bullish. The company just received EU approval. 3 analysts I know of commented last week:

- In a report released today, Edward White from H.C. Wainwright maintained a Buy rating on Karyopharm Therapeutics (KPTI), with a price target of $49.00. The company’s shares closed last Monday at $9.85, close to its 52-week low of $9.79.

- Morgan Stanley notes conditional approval, and reiterates their price target of $32.

- Karyopharm Therapeutics (KPTI) Current Valuation Underestimates Xpovio Benefit - RBC Capital. RBC Capital analyst Brian Abrahams reiterated an Outperform rating and $24.00 price target on Karyopharm Therapeutics (NASDAQ: KPTI)

A number of new investors have been added to this mailing list including some with millions of dollars of investments in KPTI. Welcome. I had several discussions with the CEO, and the President (video, and via email). And have also been in touch with the Board of Directors. A big letter was sent to the Board that some of us worked on.

I had a good 30 min Zoom chat with the CEO/co-founder, Michael Kauffman. I really like him and think he's a honest man and has integrity, and he's a scientific genius. I also had a Zoom call with his wife, Dr. Sharon Shacham who invented the company's lead drug. She's also a genius, and she's nice and a woman of integrity. She also said they realize the issue (that the founders have reached their competence limit for taking the company to the next level).

said: "I am more on your side than you know." He shared my sentiment that the company needs a new CEO. He essentially told me he knows he doesn't have the competence to be the CEO and has informed the Board. He quoted Clint Eastwood "man must know his limitations". "I can assure you that this discussion is being had with the board. Right now. and I am admitting it to you because I am with you, I'm a straight shooter".

Sounds great but it needs to happen sooner than later. Point of our letter was to outline why the transition has to be expedited. It's a classic Founder's Syndrom many of you are familiar with from some previous stocks we've discussed. But it's great that the founders in this case realize their shortcoming.

The consequence of mismanagement is best reflected in the share price. I truly believe good management can turn the company around. The CEO even cited a case where the CEO was changed and the stock took off. He pointed to the heavy weights on the Board, with experience building a 16 billion dollar company, for example, who are engaged in key talks.

The CEO also told me they had pharma interested in buying them but company told them not yet. I suppose they're back in play. Consensus is KPTI will be bought out. I told him that with all due respect I don't trust him negotiating a deal :-) He agreed :-). They have heavy weight board members. He made it very clear he's willing to let go of the "baby". I can't wait!

I anticipate change of leadership hopefully soon. If you are invested, your feedback to the Board will help because my concern is the inertial of status quo. So rattling the cages can't hurt. Let me know if you need help with that.

He assured me that the money they're spending is attached to detailed NPV analysis and they expect to have 10 times return on that investment!

Much more can be found on my page on KPTI: https://bit.ly/3sIboTt

This is not an investment advice. To be removed reply with remove. I don't add these disclaimers to every mail as y'all know them already :-)

Happy to hear your thoughts.

Happy Easter

Reza

1 APR 2021 - VERY OPTIMISTIC ANALYST PROJECTIONS

- In a report released today, Edward White from H.C. Wainwright maintained a Buy rating on Karyopharm Therapeutics (KPTI), with a price target of $49.00. The company’s shares closed last Monday at $9.85, close to its 52-week low of $9.79.

- Morgan Stanley notes conditional approval, and reiterates their price target of $32.

- Karyopharm Therapeutics (KPTI) Current Valuation Underestimates Xpovio Benefit - RBC Capital. RBC Capital analyst Brian Abrahams reiterated an Outperform rating and $24.00 price target on Karyopharm Therapeutics (NASDAQ: KPTI)

My current outlook:

§ I'll be surprised the company is not bought out before year end. Matter of how much not if. $20, $30, $50? $60 a share? Remains to be seen.

§ I expect and hope an immediate change in top leadership, with a top-notch CEO who's Wall-Street-smart, and strong track record in commercial, business, sales, alliances, relationships, building shareholder value.

§ Quarterly sales may be weak but with right management of the entire enchilada (company, market, investors, enemies, etc.) sales will improve. But new management is a must.

31 Mar 2021 - Letter to the board

I sent a letter to the Board on behalf of the activist investor group.

Received feedback today:

~~~

Hi Reza-

Our Management Team as well as our Board of Directors have received your letter.

We of course welcome feedback from our shareholders and appreciate your detailed thoughts.

If there are any follow-up questions from our Board, I will certainly let you know.

All the best-

THE SCIENTIFIC GENIUSES BEHIND KPTI'S AMAZING CANCER DRUGS

Dr. Sharon Shacham, PhD, MBA; Dr. Michael Kauffman, MD, PhD

Good. No options expiring for Sharon and Michael till 2023.

30 Mar 2021 - INVESTOR SENTIMENTS

Some investor sentiments:

"long term play. Solid science. The SP will eventually get there with sales and new indications coming in solid Tumor. I strongly predict bo of 70-125 in next 3 years. No bs."

CC transcript: "We are having a number of discussions right now, both internally and with external partners on the best way to leverage that opportunity with the pending BOSTON indication that should come hopefully by the end of this year."

I still think a molecule with this profile would be worth at least 2x current market cap to a larger pharma company.

This stock is following in Regeneron's footsteps. REGN went down consistently for 4-5 weeks, either on good news or on no news. Go figure. (It went from 14 to 470).

The only reason this news is very good is bc getting Boston approved in Europe now went from a year review to just 4 to 6 months. It is easier to pass a SNDA than it is just NDA. That could bring a suitor faster who now can ramp Europe in 2021 perhaps

Don't get trapped by shorts' stupid arguments that are for purpose of bashing the stock and getting people to sell. Just like last week they were lying about the sales force. Fact is, KPTI should be trading 3 times higher, and it will. Just a matter of at what price the big shorts will choose (or be forced) to cover. Clock is ticking on them.

Would love to wake up to a $35 BO manana

Buyout is not a matter of it but when, and how much. I bet it will be this year, whether short sellers like it or not. So the window is closing.

expecting $BMY to help accelerate the pipeline and eventually take them out. Strategically this makes sense as $BMY is developing the same pipeline indirectly in APAC (except Japan) through investment in Antengene (via Celgene investment). Celgene brought CART assets from Juno into $BMY, and might also indirectly bring in valuable XPO1/CRM1 inhibitor assets from $KPTI while also enabling breakout expansion in APAC through Antengene. Regulatory and commercial constraints would make this path for $BMY and $KPTI hardly possible, but from among a thousand ways to fail the right leadership should find a few ways to succeed.

The safest (derisked bio) in my portfolio.

$KPTI I think post-COVID that the government will bring focus to cancer research, treatments, and lift the profile and value of many oncology companies. If you research around Eric Lander who is in the news recently you will see he cofounded $VSTM where Michael Kauffman ($KPTI CEO) is on the board, and they both were on the board at $INFI a few years ago. And way back they also worked together at Millenium, which Eric founded. And when Eric Lander’s appointment (to lead the Presidential Council of Advisers on Science and Technology and the Office of Science and Technology Policy) was announced at a Pfizer facility a month ago, Mikael Dolsten was acknowledged as a founding member of Cancer Moonshot- he has been on the $KPTI board for 6 years and is Head of Research at $PFE. All of these people have a great track record with solid science that’s produced great medicines. Just some observations. Small world, no? I’ll continue to be patient with $KPTI

drug is great...pipeline is super strong.

I have owned 10 bagger nbix and they have failed repeatedly clinically but they have one commercial homerun and the stock ran from 20 to 130 after revs took off

I think the first quarter numbers will not be good, given Covid, and Kauffman as CEO, and what short interest can do to hurt the sales. But I don't mind being pleasantly surprised. But I'm looking beyond quarter one. With change leadership everything can get better. I'm a big believer in the art and science of management.

30 Mar 2021 - EUROPE APPROVED - and earlier than expected.

Karyopharm Receives Conditional Marketing Authorization from the European Commission for NEXPOVIO® (selinexor) in Combination with Dexamethasone for the Treatment of Adult Patients with Relapsed and or Refractory Multiple Myeloma

-- NEXPOVIO is the First and Only Nuclear Export Inhibitor Authorized by the European Commission --

-- Second European Regulatory Filing Based on Phase 3 BOSTON Data Expected by April 2021 --

https://investors.karyopharm.com/2021-03-29-Karyopharm-Receives-Conditional-Marketing-Authorization-from-the-European-Commission-for-NEXPOVIO-R-selinexor-in-Combination-with-Dexamethasone-for-the-Treatment-of-Adult-Patients-with-Relapsed-and-or-Refractory-Multiple-Myeloma

26 Mar 2021 - KPTI CEO's remark

The good news is he does NOT want to go it alone

"Our kid is ready for university, and we want to send him to an Ivy League." Michael Kauffman, CEO, Karyopharm, March 24, 2021. This is one of many interesting notes I picked up from the talk with Dr. K. Have to find time to type the rest of my notes.

I read a lot into the statement above in the context out of discussion with me basically pressing that we need a CEO with business forte, and he agreed and said he's talked to the Board because he recognizes his own shortcomings (he's a phenomenal scientist who's gotten approval for 3 drugs and he's really good at that). So I think a new CEO is on the way, if the company is not sold by then.

Going to university here tells me more than founders recognizing a different caliber of leadership is needed to take their baby (company) to the next level (good they realize that). To my mind, the university analogy is a very interesting analogy that depicts selling to a Pharma, and Ivy League adjective was icing on the cake ;-)

That is a sharp contrast to "We want to go it alone" that he said in 2014.

~~~

From IR:

"Sales force is around 70 which includes traditional sales reps and also a handful of what we call “Nurse Liaisons” who focus mainly on medical education. We have not changed the size since we launched last summer."

24 Mar 2021 - KARYOPHARM ACTIVIST INVESTOR GROUP

We are kicking off a KPTI activist investor group. I haven't reached out to the mailing list of about 200 investors. Some of us have been together for a long time and formed activist investor groups in the past and we were very effective. For example, we were instrumental in getting a Board of Directors of a Biotech, fire the CEO (who was buddies with the board and it was his board), fired, and disgracefully so, because he suffered from Founders' Syndrome and was not willing to let go of his "baby" and have it managed by more qualified professionals.

$KPTI "Our kid is ready for university, and we want to send him to an Ivy League." Michael Kauffman, CEO, Karyopharm, March 24, 2021. This is one of many interesting notes I picked up from the talk with Dr. K. Have to find time to type the rest of my notes.

I read a lot into the statement above in the context out of discussion with me basically pressing that we need a CEO with business forte, and he agreed and said he's talked to the Board because he recognizes his own shortcomings (he's a phenomenal scientist who's gotten approval for 3 drugs and he's really good at that). So I think a new CEO is on the way, if the company is not sold by then.

Going to university here tells me more than founders recognizing a different caliber of leadership is needed to take their baby (company) to the next level (good they realize that). To my mind, the university analogy is a very interesting analogy that depicts selling to a Pharma, and Ivy League adjective was icing on the cake ;-)

We have many tools at our disposal, including getting institutions to join us as activist investors (in the past we successfully did this too), and Board members themselves who may be sympathetic to our cause, or may act out of obligation (fiduciary duties), and last resort: legal action (e.g. derivative lawsuit).

Of course best is to always take the friendly path, which is the best and most effective, and should work when dealing with highly intelligent people. Only roadblock is ego and attachment and other psychological shortcomings, but I am cautiously optimistic, we can be an agent of positive change, and friend, rather than an adversary.

If you're an investor and like to join us, feel free to email me via this page's contact page.

Best Regards

Réza Ganjavi, MBA

WARNING TO FINANCIAL SHENANIGANS

Also, with regards to financial shenanigans manipulating the stock and options, or spreading lies about the company. You should be very careful, because we're going to kick your ass if you step out of line. We've worked with the regulators before and brought shenanigans to justice. One is in federal prison as we speak.

23 Mar 2021 - KARYOPHARM value

800 million dollar valuation is dead cheap for a company with a great approved cancer drug with a unique, new, first-in-class mechanism of action, that can be used in various cancers, and cancer rates are going up. So what gives? (see my note below on stock price). What's the fair value? I think three billion is minimal which is $40 a share. That's why Barclay has a $60 acquisition price target.

23 Mar 2021 - KPTI Stock Price

800 million dollar valuation for a company we say incredible canceled it's going to be used for other cancers as well which can be used to multiple cancers let's say dead cheap. So what gives? What's the fair value? I think three billion is minimal which is $40 a share. That's why Barclay has a $60 this year target for acquisition.

What happened to the stock price the last 2 days? You never know but reading the tea leaves, this radical drop in the stock price could be related to some factors, none of which are the core of Karyopharm story: the science -- so that's the good thing.

Many FDA PDUFA event traders didn't know that FDA approved the drug 3 months early, back in December 2020 (rare for FDA to do that and shows how important the drug is, and how much FDA likes Karyopharm's science). So the traders who buy FDA decisions bought in the days leading to last Friday, and when there was no news, they sold on Monday. I believe that may have been a reason for the big drop yesterday despite a strong biotech market day.

Then today, we heard of a couple of fucking 10b5-1 (planned sales) by the CEO and President, 4000 shares each. They still have over 1.6 million shares worth almost 18 million dollars. Michael Kauffman and Sharon Shacham will be rolling in dough when the company is sold at $40 a share which is the minimum price I see as fair. They'll have 64 million dollars! Planned sales (10b5-1's) are not extraordinary but they suck. I advised Michael and Sharon to immediately stop the planned sales, esp. in light of the fact the stock has been under short attack.

So we had that today, and a weak market day, so the stock dropped more. I sense that probably market makers took advantage of this drop and took out some stop loss orders. Watching Level 2 a bit, the stock was dropping on very thin volume.

Another factor is founders' syndrome which impacts everything. But that can change overnight.

These are the factors I can think of aside from the bigger question of why there is a big short interest and I have two theories around that topic. Sharon confirmed with me in our talk recently that it can't be because of the science. That's how strong she feels about the science. So what else could it be? I believe it could be a suitor who is having the stock manipulated so they can buy the company cheaply. It is also probably related to some management issues. I'm addressing those with Michael on a call tomorrow. I offered them some free management consulting which is my profession, and of course, I do not want to, and I will not, receive any insider information.

I have been buying more shares of KPTI yesterday and today.

I don't believe EMA is a factor in this price drop. The decision is due in 10 days. CHMP approved, and almost in every case EMA goes along with CHMP. And today's stock drop is right in sync with the overall market drop. I stand behind my theory above and not a conspiracy theory against EMA that implies leakage, corruption, etc. I wrote to someone:

I don't think it's about EMA. EMA should go with CHMP decision. Unless we get a big conspiracy theory that shorts lobbied and paid off EMA and then got insider info. The stock is moving in sympathy with markets today, and yesterday it dropped b/c PDUFA traders on Fri who didn't know about approval 3 months ago. That's how I see things.

22 Mar 2021 - analyst are very bullish

18 Mar 2021

Mailing to my investors mailing list (not investment advice)

KPTI

§ I had a 30 min zoom call with the president, Dr. Sharon Shacham. She's amazing. I'll edit the video and post more details as soon as I find the time.

§ New long positions were opened this week for April 20 and 22 calls (betting price will double next month!)

§ I suspect European approval will come in the 3 weeks. They have the CHMP thumbs up already and most drugs who get that get approved. I suspect EU partnership or RoW partnership will come unless the company is outright sold.

§ Swissmedic filing is in progress.

ALDX

"Reza,Just wanted to re-mention ALDX. I think the stock is trying to base. Company has some readouts within the 2021 year (which of course we would need positive results), Leerink just initiated a $22 price target"

ATNX

They got CRL from FDA. Stock lost 50% of its value

VYNE

VYNE now has options available.

BCRX

Dr. Joe wrote: Sold all my VYNE at a <big> loss so that I could put the money into BCRX. They report on their oral Factor D inhibitor on March 22nd. If follows through earlier results can be best in class oral factor D inhibitor (complement pathway - many possible indications) on the market. Current market cap under $2 billion with multiple approved products.

ARNA

§ Re: Olorinab, following the data JPM says company won't pursue it further. SMBC just released note saying they will not pursue it alone. So more clarity on that. They will look to partner it.

§ Even some most loyal longs are now turning on Amit Munshi. Dr. Joe wrote:

"These are the trials that Amit is responsible for the failure of:

E- Pyoderma gangrenosum

E- Primary biliary cholangitis

E- Atopic dermatitis phase 2 trial

Visceral pain olorinab phase 2a trial

Visceral pain olorinab phase 2b trial

Why would you want keep rewarding failure and then turn this guy loose on the future of this company? Time for the board to start the sale process."

§ People are still criticizing Arena's IR :-) Perhaps leftover of inept Jack Lief era IR we tried to warn them about / organizational memory, power of status quo...

§ Amit Munshi said years ago when all the cards have been turned over he'll think getting bought, but I wonder if they're really open to it given they're all in lucrative comfortable positions -- probably another company habit from Jack Lief who ran the company to the ground with mismanagement and founders' syndrome.

§ I wish Arena success. Long-suffering shareholders deserve it.

13 Mar 2021

- On Friday, I did an interview / discussion with Karyopharm's genius President / CSO. Details coming up...

- International interest in Karyopharm stock: my page gets a lot of visitors from all over the world. Just today: USA (various states), Australia, Germany, Israel, UAE, Hong Kong, Italy, Canada, Singapore, Poland, France, Switzerland.

- There is no PDUFA next Friday. No major event next Friday that we know of. Don't count on it. The approval came 3 months early in December 2020 which is very unusual and very positive; shows FDA thinks very highly of the drug. I've never seen FDA approve a drug 3 months ahead of PDUFA date.

10 Mar 2021 - partnership

-Expanded Partnership with Medidata Supports Karyopharm’s Mission to Develop First-in-Class Therapeutics

8 Mar 2021 - Europe

EMA usually goes along with CHMP. First date: CHMP. Second date: EMA approval

§ Phesgo Nov13, Dec23

§ Roclanda Nov13, Jan11

§ Xofluza Nov13, Jan 11

§ Selinexor (Nexpovio) 29 Jan. Should be approved by April 2nd.

6 Mar 2021 - KPTI UPDATE

§ I have a call scheduled with a Karyopharm's senior executive. If any of you have any questions, please send them to me via email or contact page of this site.

§ https://www.karyopharm.com/ is very informative and also lists the company's tweets on the first page (very handy).

§ Understanding the Biology of Your Cancer: Four experts discuss "New Therapies Target Multiple Myeloma's Biological Drivers"

§ Karyopharm's President, Founder, & Chief Scientific Officer, Sharon Shacham joined @PharmaVOICE on the entrepreneurs panel at the Women of the Week Virtual Event with some of industry’s most influential women!

4 Mar 2021 - SIENDO TRIAL

Phase 2 data: https://www.gynecologiconcology-online.net/article/S0090-8258(19)31663-4/fulltext

SIENDO phase 3 readout is later this year. This could be a game changer for endometrial cancer.

"We are very excited that the SIENDO study has passed its planned futility analysis and that the study will continue as planned," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "We believe this is an encouraging development for the study, and more importantly, for patients and families in need of novel treatment options for advanced or recurrent endometrial cancer. There are currently no approved therapies in the maintenance setting for patients with advanced endometrial cancer, making the future trial results from the SIENDO study, particularly important. We expect to report top-line data from this study in the second half of 2021.

4 Mar 2021 - INVESTMENT THESIS / STOCK

The stock took a dive with the rest of biotech sector. But I feel absolutely confident for my own investment purposes. Karyopharm generates revenue, its target market has just expanded, it has a strong pipeline, strong IP, EU approval should come plus partnership, Barclays Global Healthcare Conference presentation next Tuesday. And on top of my investment thesis list is:

BUYOUT.

I firmly believe Karyopharm will be bought by a big pharma in not too distant future at a nice premium. Waiting for the press release any day, but I can wait.

3 Mar 2021 - kpti update

I spoke with head of IR today. He's really good, everything we hoped Arena would have, back in the days. He puts Cindy McGee, Craig Audet, Russo and the rest of amateurish IR team in his back pocket.

Today was a tough biotech/market day. IBB is down 4%, XBI down 5%. Biotech is not for faint of heart.

But company remains very optimistic. The CEO talked about hokey-stick ramp up of sales this year.

I sent an email to top management a few days ago. They did receive it.

European approval for Nexpovio (selinexor) for Penta-Refractory Multiple Myeloma will significantly expand the market to 30 additional contries. I think approval will come by April 5 (67 days since CHMP ruling). A second filing with EMA is expected by April as well. This is an informative press release: https://investors.karyopharm.com/2021-01-29-Karyopharm-Receives-Positive-CHMP-Opinion-for-NEXPOVIO-R-selinexor-for-the-Treatment-of-Patients-with-Refractory-Multiple-Myeloma

Xpovio (selinexor) generated 76.2 million in pandemic for one small indication. In December they got approval for a much larger label. And they have a novel pipeline.

Sharon Shacham, PhD, MBA invented selinexor! Brava! She seems like a genius. She did all her studies at Tel Aviv University.

Regarding M&A, they can't comment but: "we’re not obstructionist", and "buyouts are common in this space, and at high premiums".

I increased my holding today. Couldn't resist the deep discount. I believe KPTI is significantly under-valued.

27 FEB 2021 - Discussion with Ian Karp, Karyopharm's Senior VP of Investor & Public Relations

§ I am always thrilled to see biotech companies understand the importance of IR and put a senior, credentialed professional in charge of it. Companies that do that are rewarded by better investor relations, let's say, than those who don't. I can cite a number of examples that clearly distinguish between great, mediocre, and inferior IR. I think Karyopharm is in the first category.

§ Ian is an MBA (like me, haha). Aside from leading IR, he's trusted with the entire realm of corporate communications including financial communications, corporate visibility, media relations. Again, this tells me that company's leadership takes this matter seriously, and that's excellent. Many similar companies think of IR as an inconvenience, or have it in mediocre hands, or some outsourced joint which is spread extremely thin and provides little more than lip service.

§ Ian comes from Shire which was a big pharma acquired by Takeda in 2019, but while at Shire, Ian was engaged in acquisition strategy that led to over $40B in acquisitions. I assume he'd be a good negotiator when Karyopharm will be negotiating getting bought out by a big pharma (my guess: by end of this year, for several multiples of current price). Mind you average analyst target is double current level, with some triple current level, and acquisition price set by Barclay's is $60/shares. Stock currently: $14.5

We had limited time so we went quickly over some topics. Soon after, the same day, the company appeared on a fireside chat with SVB Leerink which was very interesting (link: https://wsw.com/webcast/svbleerink47/kpti/2670592).

Short interest

We asked Ian about the short interest that's very high (20%) yet analysts are all very optimistic. Usually when there's a big short hedge fund, there's an equity research firm that's prostituting for it -- seen this many times in the past on other biotechs, where a weasel analyst sets a $1 price target on a stock that's trading at $4 to help push it down, and his big short client covers and the same short goes long by the time the stock is $50.

In KPTN's case, Ian suspects the short could be the holders of the convertible debt who would do that as a hedge: if stock goes down they profit, if the stock goes up, they're hedged by the convertible debt, and make the coupon. Makes sense.

I was wondering if there's an adverse even the shorts are waiting for. The hypothesis above discards that notion. So that's no issue. Also, having watched the stock behavior, it behaves differently than an active aggressive short trying to keep it down by drip selling, putting fake offers, getting media to prostitute for them by writing trashy articles, etc. -- I/we haven't seen that with KPTN's stock behavior, which attracted me to it.

There's been a trend to short biotechs which have launched during the pandemic. Some hedge funds are required to be short a certain %, and they're often long development stage biotechs for hopes of big gains on positive data move. So they short commercial companies whose launch may be hurting due to Covid-19. At some point that unwinds and the trend changes as the commercial efforts get more traction -- so the computers tell the hedge fund they should go long.

Analyst Coverage

All analysts have optimistic, buy rating and price targets well above current price, except Wedbush analyst who has a "hold". No analyst has a "sell" rating. That's very good!

FDA

The company received the expanded approval earlier than the March anticipated PDUFA date. It happened in December 2020.

COMPETITION

There are various drugs approved for Multiple Myeloma which is a lethal chronic cancer. Due to the availability of medicines the patients can live longer. They get a cocktail of drugs. That works for a while, then the disease comes back, then a new cocktail is given, and so on... all the drugs will get used... point is, you want to be used earlier and in more patients.

Karyopharm still made about 100M revenue last year, so there's obviously demand despite other drugs. None of the drugs cures the cancer.

The company's goals is obviously to capture more market share. So it worked on expanded indication, so doctors can prescribe it for more patients, and also duration of treatment is longer.

THE STOCK

92% of float is owned by institutions obviously foresee a positive future for the company, otherwise they would not be holding. Ian gave another great answer: There are many reasons someone would buy a company like Karyopharm, e.g., they think the company is undervalued and think the company's revenues will increase and it will do more for patients and do better financially and that translated into higher value.

Fortunately Karyopharm's drug works for many kinds of cancers so a lot of their spend is to test the drug in other kinds of cancers, and for combination with other drugs. So studies that show the drug works in combination can prove very lucrative.

EU APPROVAL

CHMP issued positive opinion. EU approval is expected by April. The idea of going it alone in EU is out. They are in discussions with potential partners / collaborators in Europe and Japan. They expect large revenue in Europe by end of this year, assuming approval in April.

Already, multiple myeloma treatment guidelines developed by the European Hematology Association (EHA) and European Society for Medical Oncology (ESMO) added SVd* as a treatment option in the second line setting and Sd** for patients with triple-class refractory disease.

PARTNERSHIPS

Company has already inked partnerships for China, South Korea, Taiwan, Australia and other countries in that region, Israel, Palestinian Authority, Canada. Europe and Japan, coming up.

BUYOUT

This is a good time in my opinion for a Big Pharma which already has the infrastructure to buy Karyopharm out. A few billion dollars is peanuts for a Big Pharma.

UPCOMING CATALYSTS IN 2021

1. EMA conditional approval based on STORM data

2. EMA submission of BOSTON study data (Type II variation)

3. Increased U.S. XPOVIO sales following expanded FDA approval in multiple myeloma

4. SIENDO Phase 3 study fully enrolled and topline data announced

5. EMA expanded approval based on BOSTON study

6. Initiation of Phase 3 study evaluating XPOVIO + pomalidomide in patients with multiple myeloma

7. Initiation of Phase 2 study evaluating XPOVIO + pembrolizumab in patients with metastatic melanoma

8. Additional combination data with XPOVIO and other standard of care anti-cancer drugs to be presented at key medical meetings

9. Continued, increased U.S. XPOVIO sales

24 FEB 2021 - KPTI RESEARCH

§ KPTI seems to have a lot going for it including a very rich pipeline addressing various diseases including multiple myeloma which is a common type of deadly blood cancer. This is a very informative paragraph about Karyopharm:

In July 2019, the US Food and Drug Administration (FDA) approved selinexor (XPOVIO®) in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (rrMM) and in June 2020 approved selinexor (XPOVIO®) as a single-agent for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). In December 2020, selinexor (XPOVIO®) also received FDA approval as a combination treatment for multiple myeloma after at least one prior therapy. Selinexor (XPOVIO®) is so far the first and only oral SINE compound approved by the FDA and is the first drug approved for the treatment of both MM and DLBCL. Selinexor (XPOVIO®) is also being evaluated in several other mid-and later-phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer...

and so on-- read full text here: https://www.prnewswire.com/news-releases/antengene-announces-nda-for-atg-010-selinexor-granted-priority-review-by-chinas-nmpa-301234036.html which is the announcement for:

Antengene Announces NDA for ATG-010 (Selinexor) Granted Priority Review by China's NMPA

"rrMM still remains an incurable disease and we are excited that more patients may have access to ATG-010 earlier in the course of their treatment.

§ Last quarterly results

Karyopharm Q4 topline shines, expects XPOVIO sales growth

Revenues: $35.1M (+93.9%); Xpovio Sales: $20M; License and other revenue: $14.8M.

Q1 Outlook: Expects XPOVIO sales to return to growth beginning in the first quarter of 2021.

Cash, cash equivalents, restricted cash and investments as of December 31, 2020 totaled $276.7M.

The company said that the clinical development of XPOVIO in solid tumor indications continues to advance, with top-line data from the Phase 3 SIENDO study in endometrial cancer expected in the second half of 2021.

§ (Feb 2021) H.C. Wainwright Thinks Karyopharm Therapeutics’ Stock is Going to Recover and has price target of $49 and Buy rating.

§ KPTI sitting atop Barclay's M&A list (Dec 2020) Barclay's has a list of candidates for M&A and Karyopharm is the first one on the list with average share price of $60. Barclay's current price target is $31.

§ Jefferies TV segment. Ripe for short squeeze... KPTI has very high short interest and strong fundamentals.

"It's a product story. There's revenue here. It's an oncology company launching drugs into a pretty big market. They're looking for earlier lines therapy etc. etc. - so there is something here to back up the valuation unless so many high flyers that are dream stocks. KPTI has real revenue and earnings and real pipeline... launching during Covid was hard for all companies... but it's interesting anyway." https://www.cnbc.com/video/2021/02/04/reddit-playing-a-major-role-in-biotech-trading-action-says-jefferies-top-health-care-analyst.html

22 FEB 2021 - KPTI INITIATION

I was feeling uncomfortable about VYNE over the weekend because I remembered what happened to Arena after approval of Belviq and weak sales. What worries me in the short term is if the pandemic drags on and scrips don't get traction, and the hedgies see that because they have access to weekly sales data and we don't, they could smell blood and attack VYNE like they attacked ARNA, which is easier to do now that the stock is 8 something instead of 1 or 2 something.

So I thought about this a lot. I like VYNE's science, potential market and they have cash. So did Arena, but VYNE's management is incomparable to Arena's back then, which sucked (talking about 2012 to 2017, 5 painful years that some of you remember.

So I chickened out and sold most of my shares at a loss today. I have a few shares to keep an eye on it, and I'll follow the company out of interest, and when prescriptions go up and pandemic goes down, I can get back in. The risk is mine. Maybe it'll take off by then, but that's a choice I made so I live with the consequence :-)

Karyopharm Therapeutics (KPTI)

I've also been following KPTI closely and my liking for the company and the stock's characteristics grew. So I picked up some KPTI today. It's a Massachusetts company focusing on treatments of cancer (e.g. multiple myeloma) and other diseases.

§ Average analyst target: $30

§ Current price: $15

§ 94% owned by institutions (I really like this fact)

§ 10% owned by insiders (that's a lot for a small biopharma)

§ 20% short interest (that's huge, which means good news can start a short squeeze)

§ I sold a few calls against some of the shares I bought today. March 17.50 calls were grabbed instantly (probably by the shorts as hedge -- they think the stock may go to $18 in a month).

§ Enterprise value of almost a billion. I've read they could be a takeover target. I can imagine a big pharma moving in for spare change (3 billion).

§ They already have approval and generating revenue (around $100 million last year).

This is what Dr. Vig wrote in his last update:

§ KPTI karyopharm .com selinexor oral drug for multiple myeloma and likely other cancers, already approved for late stage myeloma and will likely get approved for earlier stage myeloma with pdufa march 19,2021, got approval for lymphoma in June 2020, they were testing selinexor for hospitalized covid 19 patients since selinexor has antiviral and anti inflammatory properties, working on liposarcoma and uterine cancer and lung cancer and glioblastoma as well.

As always, do your own research.

Best wishes

Reza Ganjavi

PS --I just share my research, and I do not provide investment advice.