Bristol Myers Squibb (BMY)

[DewDiligence]

Opdivo monotherapy shows statsig RFS in adjuvant melanoma (fully resected Stage IIB/C):

https://finance.yahoo.com/news/bristol-myers-squibb-announces-adjuvant-105900730.html

These results are from the phase-3 CHECKMATE-76K trial. Details to be presented at a medical conference.

[joe_techi]

https://biopharma.media/deucravacitinib-miracle-drug-for-autoimmune-diseases-1094/

Hangs a bit but loads

[DewDiligence]

What is the link for that? TIA

[joe_techi]

Sotyktu: Miracle Pill for Autoimmune Diseases

"Given both deucravacitinib’s new mechanism of action and its very acceptable safety profile, it has the ability to make billions of dollars for Bristol-Myers Squibb. Well, it will give immeasurably suffering patients an extra chance for healing.

For U.S. patients, the price of Sotyktu is set at $6,146 (excluding discounts and rebates) for a one-month course of treatment. A year’s worth of therapy would cost $74,000. This is one-third more than the cost of treating psoriasis with Otezla (apremilast).

According to industry forecasts, deucravacitinib sales will reach $2.4 billion annually by 2026. Peak demand for deucravacitinib will easily reach $4 billion annually."

https://biopharma.media/deucravacitinib-miracle-drug-for-autoimmune-diseases-1094/

[DewDiligence]

Perfect timing—BMY reports 2yr Sotyktu data in psoriasis at EADV conference:

https://finance.yahoo.com/news/bristol-myers-squibb-announces-sotyktu-063000160.html

[DewDiligence]

FDA approves Sotyktu (deucravacitinib) for psoriasis:

https://investors.bms.com/iframes/press-releases/press-release-details/2022/U.S.-Food-and-Drug-Administration-Approves-Sotyktu-deucravacitinib-Oral-Treatment-for-Adults-with-Moderate-to-Severe-Plaque-Psoriasis/default.aspx

The label does not include JAK-like black-box warnings or usage restrictions, validating BMY’s contention that Sotyktu's TYK2 target is well differentiated from JAK1/2/3.

BMY expects eventual Sotyktu approval in other autoimmune indications and foresees peak annual sales of at least $4B.

[DewDiligence]

BMY/JNJ—Milvexian phase-2 data in treatment of acute ischemic stroke…

PR:
https://finance.yahoo.com/news/breaking-results-phase-2-axiomatic-073600645.html

CC slides:
https://s21.q4cdn.com/104148044/files/doc_presentations/2022/Bristol-Myers-Squibb-ESC-IR-2022-Event-Presentation.pdf

Milvexian is an oral inhibitor of Factor XIa being co-developed by BMY and JNJ (#msg-140083631). For BMY specifically, Milvexian is the company’s hope for replacing Eliquis revenue when Eliquis goes off-patent in 2028.

In the trial reported today, Milvexian + Plavix/aspirin was compared to Plavix/aspirin alone at five different Milvexian doses. Despite the lackluster results, which include a flat dose response, BMY/JNJ have committed to a phase-3 program for Milvexian in three indications: secondary stroke prevention; ACS; and primary stroke prevention in patients with AF. The phase-3 trials are slated to start by year-end 2022 (see slide #13). Curiously, the three phase-3 indications do not include either of the indications tested in phase-2, which are treatment of acute ischemic stroke (see above) and VTE prevention (#msg-166773814).

The main competition for Milvexian is Bayer’s Asundexian, another oral FXIa inhibitor that just started phase-3 trials in AF/stroke prevention and treatment of acute ischemic stroke (https://www.businesswire.com/news/home/20220828005030/en ).

BMY has pegged Milvexian is a $5B+ opportunity (not risk adjusted—see slide #20), but this seems optimistic in light of the dataset released today.

[DewDiligence]

Opdivo/Yervoy misses DFS primary endpoint in adjuvant RCC:

https://www.businesswire.com/news/home/20220728006068/en

This result is from Part A of the CHECKMATE-914 study, where Opdivo/Yervoy was compared to placebo. Part B of the same study, which compares Opdivo monotherapy to placebo, is still in progress.

[DewDiligence]

BMY 2Q22 CC transcript:

https://www.fool.com/earnings/call-transcripts/2022/07/27/bristol-myers-squibb-bmy-q2-2022-earnings-call-tra

[DewDiligence]

BMY 2Q22 CC slides:

https://s21.q4cdn.com/104148044/files/doc_presentations/2022/BMY-2022-Q2-Results-Investor-Presentation.pdf

[DewDiligence]

BMY 2Q22 results:

https://news.bms.com/news/corporate-financial/2022/Bristol-Myers-Squibb-Reports-Second-Quarter-Financial-Results-for-2022/default.aspx

2022 non-GAAP EPS guidance remains $7.44-7.74.

[DewDiligence]

CHMP approves Opdulag for first-line melanoma:

https://finance.yahoo.com/news/bristol-myers-squibb-receives-positive-105900006.html

Opdulag, an FDC of Opdivo and Relatlimb (anti-LAG-3), received FDA approval in this indication in Mar 2022 (#msg-168259775).

[DewDiligence]

BMY sets all-time intraday and closing highs.

The CELG-CVR lawsuit didn’t make a dent, evidently.

[DewDiligence]

FDA approves BMY’s Breyanzi for second-line LBCL:

https://www.businesswire.com/news/home/20220427005982/en

The approval is based on phase-3 data reported one year ago, in which Breyanzi showed statsig-superior EFS compared to SoC (#msg-164317285).

Breyanzi will compete in this newly approved indication with GILD’s Yescarta (#msg-167110232).

Breyanzi was initially FDA-approved for third-line LBCL in Feb 2021 (#msg-161552697). This is the drug at the heart of the lawsuit by former CELG shareholders (#msg-169238809).

[DewDiligence]

BMY withdraws Reblozyl sBLA in beta thalassemia:

https://investors.bms.com/iframes/press-releases/press-release-details/2022/Bristol-Myers-Squibb-Withdraws-Supplemental-Biologics-License-Application-sBLA-for-Reblozyl-luspatercept-aamt-for-Non-transfusion-Dependent-NTD-Beta-Thalassemia/default.aspx

The Company could not appropriately address the U.S. Food and Drug Administration’s questions about the benefit-risk profile of Reblozyl in this patient population based on the current dataset from the Phase 2 BEYOND trial.

[DewDiligence]

BMY acquires TPTX for $76.00 cash—a 122% premium to yesterday’s close:

https://www.businesswire.com/news/home/20220603005198/en

As a result of the acquisition, BMY is reducing 2022 non-GAAP EPS guidance by $0.08 plus a charge for in-process R&D to be determined later. (BMY’s prior 2022 non-GAAP EPS guidance was $7.44-7.74.)

[DewDiligence]

IMTX, BMY expand oncology collaborations (plural):

https://finance.yahoo.com/news/immatics-bristol-myers-squibb-expand-105900729.html

• New multi-program collaboration to develop allogeneic TCR-T/CAR-T programs brings together Immatics’ allogeneic gamma delta T cell therapy platform ACTallo with Bristol Myers Squibb’s technologies and oncology drug development expertise

• Immatics to receive upfront payment of $60 million and additional milestone payments of up to $700 million per program plus tiered royalty payments of up to low double-digit percentages on net product sales across multiple programs under the new collaboration

• Per 2019 agreement, Bristol Myers Squibb to also add one additional autologous TCR-T target where Immatics will receive an upfront payment of $20 million and be eligible for milestone payments and royalties

[DewDiligence]

BMY will_advance Deucravacitinib to_phase-3_in lupus, based on phase-2 data presented at EULAR:

https://www.businesswire.com/news/home/20220531005751/en

Deucravacitinib is under FDA and EMA review in psoriasis; the PDUFA date is 9/10/22 (#msg-166931026).

[DewDiligence]

FDA approves Opdivo/chemo and Opdivo/Yervoy in_first-line esophageal cancer_regardless_of_PD-L1_status:

https://finance.yahoo.com/news/u-food-drug-administration-approves-221100701.html

These approvals are based on the CHECKMATE-648 study. See #msg-164194868 for details.

[DewDiligence]

Synopsis of MRK's (anti-LAG-3) favezelimab data from ASCO abstract:

https://www.biopharmadive.com/news/asco-merck-favezelimab-lag3-hodgkin-trial/624457/

Favezelimab might eventually compete with BMY’s Opdualag (#msg-168259768), but it has a long way to go.

Please see #msg-168259803 and https://twitter.com/DewDiligence/status/1395141087413538822 for related info.

[DewDiligence]

BMY’s lineup at ASCO and EHA:

https://finance.yahoo.com/news/bristol-myers-squibb-data-asco-105900815.html

[DewDiligence]

Opdivo/Yervoy failed to show statsig-superior OS compared to chemotherapy in first-line bladder cancer in patients with PD-LI>=1%:

https://finance.yahoo.com/news/bristol-myers-squibb-provides-checkmate-105900892.html

MRK’s Keytruda and Roche’s Tecentriq have also whiffed in this setting.

[DewDiligence]

BMY buys worldwide commercial rights to BBIO’s BBP-398:

https://www.globenewswire.com/news-release/2022/05/12/2441841/0/en/BridgeBio-Announces-Exclusive-License-Agreement-with-Bristol-Myers-Squibb-to-Develop-and-Commercialize-BBP-398-a-Potentially-Best-in-Class-SHP2-Inhibitor-in-Oncology.html

Under the terms of the agreement, BridgeBio will receive an upfront payment of $90 million, up to $815 million in development, regulatory and sales milestone payments, and tiered royalties in the low- to mid-teens. BridgeBio will retain the option to acquire higher royalties in the United States in connection with funding a portion of development costs upon the initiation of registrational studies.

Based on the terms of the agreement, BridgeBio will continue to lead its ongoing Phase 1 monotherapy and combination therapy trials. Bristol Myers Squibb will lead and fund all other development and commercial activities.

[DewDiligence]

BMY extends/expands drug-discovery collaboration with EVO:

#msg-168811996

[DewDiligence]

1Q22 CC transcript:

https://www.fool.com/earnings/call-transcripts/2022/04/29/bristol-myers-squibb-bmy-q1-2022-earnings-call-tra/

[DewDiligence]

BMY 1Q22 results:

PR:
https://news.bms.com/news/corporate-financial/2022/Bristol-Myers-Squibb-Reports-First-Quarter-Financial-Results-for-2022/default.aspx

CC slides:
https://s21.q4cdn.com/104148044/files/doc_presentations/2022/BMY-2022-Q1-Results-Investor-Presentation.pdf

2022 non-GAAP EPS was lowered by $0.21 due to an FASB accounting change regarding in-process R&D (i.e. accounting for acquisitions). The updated range for 2022 non-GAP EPS (unchanged other than the item described above) is $7.44-7.74.

[DewDiligence]

FDA approves BMY’s Camzyos (mavacamten) for obstructive hypertrophic cardiomyopathy:

https://news.bms.com/news/corporate-financial/2022/U.S.-Food-and-Drug-Administration-Approves-Camzyos-mavacamten-for-the-Treatment-of-Adults-With-Symptomatic-New-York-Heart-Association-Class-II-III-ObstructiveHypertrophic-Cardiomyopathy-HCM-to-Improve-Functional-Capacity-and-Symptoms/default.aspx

BMY thinks Camzyos will have peak annual sales of at least $4B. This is the drug BMY got in the $13.1B acquisition of MYOK in Oct 2020 (#msg-158698900).

[Cosa]

Looks like it's starting to rollover.

[DewDiligence]

NKTR -24%/AH on_termination_of Bempeg program following phase-3 failures in RCC and bladder cancer:

https://finance.yahoo.com/news/nektar-bristol-myers-squibb-announce-203000621.html

Nektar Therapeutics and Bristol Myers Squibb (NYSE: BMY) today announced that based on results from pre-planned analyses of two late-stage clinical studies of bempegaldesleukin (BEMPEG) in combination with Opdivo (nivolumab) in renal cell carcinoma (RCC) and bladder cancer, the companies have jointly decided to end the global clinical development program for bempegaldesleukin in combination with Opdivo. These studies and all other ongoing studies in the program will be discontinued.

Bempeg previously failed in a phase-3 trial in combination with Opdivo in melanoma (#msg-168191364), so today’s news is three strikes and you’re out!

Rarely has a cancer drug failed so utterly and completely to live up to initial expectations (#msg-138532013). NKTR’s share price is down 96%(!) from its 2018 high.

BMY is trading flat in the AH session.

[DewDiligence]

BMY presents full dataset from CHECKMATE-816 trial in neoadjuvant NSCLC:

https://finance.yahoo.com/news/neoadjuvant-opdivo-nivolumab-chemotherapy-significantly-151500888.html

Opdivo/chemo received FDA approval in this indication one month ago, based on the above data (#msg-168093570).

[DewDiligence]

EU approves three new Opdivo indications…

1. Opdivo + chemo in first-line esophageal cancer with PD-L1>=1% (based on CHECKMATE-648):
https://finance.yahoo.com/news/bristol-myers-squibb-receives-european-105500913.html

2. Opdivo + Yervoy in same indication as above (also based on CHECKMATE-648):
https://finance.yahoo.com/news/bristol-myers-squibb-receives-european-105000567.html

3. Opdivo monotherapy in adjuvant MIUC with PD-L1>=1% (based on CHECKMATE-274):
https://finance.yahoo.com/news/bristol-myers-squibb-receives-european-104500445.html

[lettruthringout]

Updated Cumulative Results Of Treatment With Mavacamten

https://www.acc.org/Latest-in-Cardiology/Articles/2022/04/02/13/22/Sun-945am-Treatment-Mavacamten-acc-2022

[lettruthringout]

Certainly BMY never would've parted with China franchise.

[BMY] may be eligible to receive regulatory and sales milestone payments of up to $147.5 million, as well as tiered double-digit royalties on the sale of mavacamten in the [China] territories outlined as part of the collaboration.

Lian is happy to let BMY do all the heavy lifting. Go BMY!

[DewDiligence]

… [BMY] may be eligible to receive regulatory and sales milestone payments of up to $147.5 million, as well as tiered double-digit royalties on the sale of mavacamten in the [China] territories outlined as part of the collaboration. LianBio will fund all development and commercial expenses in the collaboration territory.

https://www.lianbio.com/news/myokardia-and-lianbio-form-strategic-partnership/

[lettruthringout]

LianBio might be better play for mavacamten

https://www.investorvillage.com/smbd.asp?mb=2294&mn=8977&pt=msg&mid=23095516

[DewDiligence]

BMY’s reports detailed Mavacamten data from phase-3 VALOR trial:

https://www.businesswire.com/news/home/20220401005495/en

Bristol Myers Squibb today announced results from the Phase 3 VALOR-HCM study, which showed the addition of mavacamten, an investigational, first-in-class cardiac myosin inhibitor, significantly reduced the need for septal reduction therapy (SRT) in patients with severely symptomatic obstructive hypertrophic cardiomyopathy (obstructive HCM) who had been appropriate for SRT per the 2011 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines at baseline. Study participants were on maximally tolerated background regimens when they entered the trial and remained on them through the duration of the study. These data were presented today as a late-breaking clinical trial at the American College of Cardiology’s 71st Annual Scientific Session.

At 16 weeks the primary and all secondary endpoints were met. Of patients treated with mavacamten, 82% had not proceeded with SRT and no longer met the criteria for SRT according to the 2011 ACC/AHA Guidelines compared to 23% of patients receiving placebo.

BMY announced in Feb 2022 that this trial net its primary/secondary endpoints (https://www.businesswire.com/news/home/20220215005925/en ), but the details hadn’t been disclosed until today’s ACC meeting.

Mavacamten is under FDA review for a less-sick population with obstructive HCM; the PDUFA date for that indication is 4/28/22.

BMY acquired Mavacamten in the 2020 buyout of MYOK for $13.1B (#msg-158698900). BMY thinks Mavacamten will become a $4B/year drug in due course.

[Cosa]

I just grabbed a few puts for September. Looking at 10 year chart, every time it hit new highs there was a pull back. Just a little gamble. Definitely a good company to own shares in.

[DewDiligence]

Reblozyl sBLA in beta thalassemia PDUFA extended three months to 6/27/22 due b/c additional data was submitted during the review:

https://finance.yahoo.com/news/bristol-myers-squibb-announces-prescription-105900565.html

[DewDiligence]

BMY inks oncology-drug-discovery collaboration with (private) Volastra Therapeutics:

https://www.biospace.com/article/releases/volastra-therapeutics-announces-drug-discovery-collaboration-with-bristol-myers-squibb/

$30M up-front cash; $1.1B biobucks.

[DewDiligence]

Addendum—BMY has projected $4B+ peak sales of Opdualag by 2029.

FDA label:
https://t.co/R7v5xodScz

[DewDiligence]

FDA approves Opdualag—a_co-formulated_FDC_of Opdivo and anti-LAG-3 relatlimab—in first-line melanoma:

https://www.businesswire.com/news/home/20220304005561/en

The approval is based on the RELATIVITY-047 trial, which tested Opdivo + relatlimab against Opdivo monotherapy and had a PFS HR=0.75 (#msg-163914232).

In first-line melanoma, Opdulag offers comparable efficacy to Opdivo + Yervoy with less toxicity.

My abbreviated take:
https://twitter.com/DewDiligence/status/1395141087413538822

[DewDiligence]

BMY sues AZN claiming Imfinzi infringes Opdivo patent:

https://finance.yahoo.com/news/bristol-myers-sues-astrazeneca-over-172412187.html

https://tmsnrt.rs/3ieYLvz

[DewDiligence]

Keytruda monotherapy-vs-placebo DFS HR=0.76 in adjuvant* NSCLC, irrespective of PD-L1 status, in phase-3 KEYNOTE-091 trial:

https://www.businesswire.com/news/home/20220317005084/en

Although the DFS endpoint was statig, the effect size was so-so (HR=0.76). The statsig outcome was reported on 1/10/22 (https://www.merck.com/news/mercks-keytruda-pembrolizumab-showed-statistically-significant-improvement-in-disease-free-survival-versus-placebo-as-adjuvant-treatment-for-patients-with-stage-ib-iiia-non-small-cell/ ), but the details were not disclosed until today.

Curiously, in the pre-specified subgroup with PD-L1>=50%, Keytruda’s DFS compared to placebo had a non-statsig HR=0.82—a worse result than in the overall trial.

The HR for OS, a secondary endpoint that is not yet mature, was 0.87.

All told, this is not a great dataset, IMO, but it may be enough for FDA approval. These data may put Keytruda at a competitive disadvantage to Tecentriq and Opdivo in early-stage NSCLC.

*Stage 1b-IIIa.

[DewDiligence]

NKTR’s Bempeg fails as addend to Opdivo in first-line melanoma:

https://finance.yahoo.com/news/bristol-myers-squibb-nektar-announce-105900961.html

Bristol Myers Squibb and Nektar Therapeutics today announced an update following the first analysis of the Phase 3 PIVOT IO-001 study evaluating the doublet therapy of bempegaldesleukin in combination with Opdivo (nivolumab) compared to Opdivo monotherapy as a first-line treatment for previously untreated unresectable or metastatic melanoma. Following a review of the study for efficacy and safety by an independent Data Monitoring Committee (DMC), Bristol Myers Squibb and Nektar were informed that the study did not meet the primary endpoints of progression-free survival (PFS) and objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR). The DMC notified the companies that the third primary endpoint of overall survival (OS) did not meet statistical significance at the first interim analysis.

Given there was no additional clinical benefit in the doublet therapy arm compared to the monotherapy arm for the primary endpoints of PFS and ORR, and based on the data reviewed by the DMC, the companies have decided to unblind the trial and to perform no additional analyses for the OS endpoint.

Additionally, based on the results from PIVOT IO-001, the companies have also made the decision to discontinue enrollment and unblind the ongoing PIVOT-12 study in adjuvant melanoma, which is evaluating the doublet therapy of bempegaldesleukin in combination with Opdivo compared to Opdivo monotherapy in patients at high risk for recurrence after complete resection of melanoma.

[DewDiligence]

TEVA launches first US generic Revlimid—but the generic volume is constrained by a prior patent settlement between CELG and Allergan (#msg-119362355):

The volume limit is expected to be a mid-single-digit percentage of the total lenalidomide capsules dispensed in the United States during the first full year of entry. The volume limitation is expected to increase gradually each 12 months until March of 2025, and is not expected to exceed one-third of the total lenalidomide capsules dispensed in the U.S. in the final year of the volume-limited license [i.e. Apr 2026-Apr 2027] under this agreement.

This is why BMY’s guidance for 2022 Revlimid sales is still $9.5-10B (vs $12.8B in 2021: #msg-167758757), declining about $1.5B per year during 2023 and beyond.

TEVA’s PR today:
https://finance.yahoo.com/news/teva-announces-launch-first-generic-130000463.html

Note: TEVA acquired generic Revlimid from Allergan in 2016 (#msg-124264340).

[DewDiligence]

FDA approves Opdivo/chemo in neoadjuvant* NSCLC, irrespective of PD-L1 status:

https://www.businesswire.com/news/home/20220301006264/en

This is a large potential market and Opdivo is the only FDA-approved immunotherapy in the NSCLC neoadjuvant setting (i.e. before surgical resection).

The approval is based on the CHECKMATE-816 study, where Opdivo/chemo bested chemo alone with the HR for EFS=0.63. Additionally, 24% of patients in the Opdivo/chemo arm had a pathological complete response (no detectable cancer) vs 2% in the chemo-only arm.

OS, which was not a primary endpoint in this trial, had an impressive HR=0.57; however, so little alpha was allocated to OS in the statistical analysis plan that the HR=0.57 result was not deemed statsig.

*Stage Ib, II, or IIIa.

[DewDiligence]

Opdivo sBLA in resectable NSCLC has 7/13/22 PDUFA date (with FDA priority review):

https://www.businesswire.com/news/home/20220225005538/en

[DewDiligence]

BHVN licenses SMA drug candidate—taldefgrobep alfa (a/k/a BMS-986089) from BMY for undisclosed milestone payments and royalties:

https://finance.yahoo.com/news/biohaven-licenses-taldefgrobep-alfa-phase-115000615.html

Under the terms of the agreement, Biohaven will receive worldwide rights to taldefgrobep and Bristol Myers Squibb will be eligible for regulatory approval milestone payments, as well as tiered, sales-based royalties beginning in the high teens.

This drug previously failed in clincial trials run by BMY/Roche, so BHVN must have a new angle.

[DewDiligence]

CHMP approves three new Opdivo indications with PD-L1 expression >=1%...

Opdivo monotherapy in adjuvant MIUC:
https://www.businesswire.com/news/home/20220223006231/en

Opdivo/Yervoy in first-line esophageal:
https://www.businesswire.com/news/home/20220224006058/en

Opdivo/chemo in first-line esophageal:
https://www.businesswire.com/news/home/20220224006066/en

[DewDiligence]

Mavacamten phase-3 succeeds in patients with obstructive HCM eligible for septal reduction therapy:

https://www.businesswire.com/news/home/20220215005925/en

Note: The above is a narrower indication than the one BMY is seeking in the existing NDA that has a 4/28/22 PDUFA date.