Lattice miss is grating for Bristol Myers

 Why deucravacitinib would fail in ulcerative colitis when it succeeded convincingly in psoriasis is not clear, but fail it has. In the phase 2 Lattice-UC study Bristol Myers Squibb’s oral Tyk2 inhibitor did not show improved clinical remission over placebo in moderate to severe UC. Neither did the trial meet its secondary efficacy endpoints. Deucravacitinib might still have a chance in the condition: a second phase 2 trial testing a higher dose is under way, and could report imminently. But hopes in UC will surely dim, not least because Pfizer has already discontinued its Tyk2, PF-06826647, in the disease. Perhaps deucravacitinib is a better bet in the various other disorders in which it is being trialled, though for now psoriasis remains the only indication for which analysts are forecasting sales – $2.4bn in 2026, according to Evaluate Pharma. The news will hardly help shore up confidence in Bristol’s biggest pipeline hope, which has already been dented by regulatory concerns. The company’s shares have slid heavily since the FDA slapped surprisingly stringent warnings on the related Jak-inhibitor class, with investors fearful that the regulator might consider the Tyk2 mechanism to carry similar risks.

Selected clinical-stage projects targeting Tyk2
Project	Company	Status	Trial details
Deucravacitinib (BMS-986165)	Bristol Myers Squibb	Psoriasis (ph3)	Poetyk-PSO-1 (NCT03624127) and Poetyk-PSO-2 (NCT03611751) hit
		Psoriatic arthritis (ph3)	NCT04908202 and NCT04908189, end 2023
		Ulcerative colitis (ph2)	Lattice-UC (NCT03934216) failed; IM011-127 (NCT04613518) ends 2021
		Crohn's disease (ph2)	NCT03599622, ends 2023
		Lupus nephritis (ph2)	NCT03943147, ends 2023
		Systemic lupus erythematosus (ph2)	NCT03920267, ends 2023
PF-06826647	Pfizer	Psoriasis (ph2)	NCT03895372, completed by no results reported
		Hidradenitis suppurativa (ph2)	NCT04092452, ends 2022 (includes brepocitinib & PF-06650833 arms)
Topical brepocitinib (PF-06700841)*	Pfizer	Atopic dermatitis (ph2)	NCT03903822, hit Mar 2021
		Psoriasis (ph2)	NCT03850483, ends 2021
Oral brepocitinib (PF-06700841)*	Pfizer	Psoriatic arthritis (ph2)	NCT03963401, completed but no results reported
		Systemic lupus erythematosus (ph2)	NCT03845517, ends 2022
		Hidradenitis suppurativa (ph2)	NCT04092452, ends 2022 (also includes PF-06826647 & PF-06650833 arms)
		Vitiligo (ph2)	NCT03715829, completed, no results (also includes ritlecitinib (PF-06651600) arm)
		Crohn's disease (ph2)	NCT03395184, ends 2022 (also includes ritlecitinib (PF-06651600) arm)
NDI-034858	Nimbus^	Plaque psoriasis (Ph2)	NCT04999839, ends 2022
OST-122**	Oncostellae	Ulcerative colitis (ph1/2)	NCT04353791, ends 2022
ICP-332	Innocare	Ph1 in healthy volunteers	Trial begun in China
BMS-986322	Bristol Myers Squibb	Ph1 in healthy volunteers	NCT04175925, recruitment on hold owing to Covid-19
Notes: *also hits Jak1; **also hits Jak3 & ARK5; ^Bristol Myers Squibb has option via Celgene acquisition. Sources: Evaluate Pharma, clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/snippets/lattice-miss-grating-bristol-myers

Takeda gets the pipeline blues

 Takeda’s 11% or $3.3bn loss in value yesterday, owing to the halt of the phase 2 narcolepsy project TAK-994 on a toxicity signal, seemed overdone. However, a look at the company’s pipeline shows that TAK-994 had relatively high hopes attached, and it is hard to get excited about some of the other contenders.

The stumble comes hot on the heels of the failure of pevonedistat, which had been another key component of Takeda’s R&D engine. The Japanese group will only come under more pressure to replace its biggest seller, Entyvio, as that drug’s 2026 patent expiry creeps closer, and the latest setbacks will have dented confidence in its strategy.

A more pressing problem is the loss of exclusivity for the ADHD drug Vyvanse in 2023. Perhaps Takeda will make a foray into M&A to restock its pipeline, and now might be a good time with valuations lower than they have been in recent years.

 Oncology (Ninlaro, Adcetris, Leuplin): $3 759m

Takeda has plenty of R&D projects, the table below shows. The issue might be quantity over quality, sellside consensus sales forecasts compiled by Evaluate Pharma suggest.

It looks unlikely that the oral orexin agonist TAK-994 will be part of Takeda’s future, although the group did not give details on the issue that spurred it to stop two phase 2 trials.

The toxicity signal also raises doubts about the company’s two other orexin agonists, TAK-861 and TAK-925. The only other group with clinical-stage assets that act on this target, according to Evaluate Pharma, is NLS Pharmaceutics, whose extended-release formulation of mazindol is in phase 2 for narcolepsy.

If TAK-861 and TAK-925 also fall by the wayside, Takeda’s neuroscience pipeline will look sparse. Other assets here include the Ovid-originated rare epilepsy contender soticlestat, to which the Japanese company picked up rights this year, TAK-071 in Parkinson’s, and earlier-stage projects in Parkinson’s and depression.

Most valuable

According to the sellside, the group’s most valuable project by 2026 revenues is the dengue vaccine TAK-003, which is due an EU CHMP opinion by the end of the year. The jab is expected to eclipse Sanofi’s FDA-approved dengue vaccine Dengvaxia, but there have been concerns about waning efficacy with TAK-003. And a tropical disease vaccine is never going to be a huge money spinner.

Takeda is offloading another vaccine candidate, the norovirus shot TAK-214, to a new joint venture known as Hillevax.

Meanwhile, the Arrowhead-partnered hep B asset ARO-AAT/TAK-999 has shown promise in alpha-1 antitrypsin deficiency, but it is still early days.

In oncology, hopes are high for the Car-NK cell therapy project TAK-007; however, this field is growing crowded. Takeda’s other mid-stage cancer candidates are the T-cell engager TAK-186, gained via the buyout of Maverick Therapeutics, and TAK-981, a Sumo inhibitor – Takeda appears to be the only group targeting this mechanism.

True, Takeda has just bagged approval for Exkivity in EGFR exon 20 insertion-positive NSCLC, but this is a niche use and the drug is only expected to bring in $436m by 2026.

With so many irons in the fire, it might not be time for Takeda to panic just yet. But the pipeline needs to start delivering results soon.

Takeda's mid-to-late-stage pipeline
Product	Description	Status	2026e sales ($m)	NPV ($m)
Filed
TAK-003	Dengue virus vaccine	Filed in EU; US filing due H2 2021	531	1,455
Maribavir (TAK-620)	CMV protein kinase inhibitor for post-transplant CMV infection	Filed in US & EU	354	1,118
Eohilia (TAK-721)	Topical corticosteroid for eosinophilic oesophagitis	April Pdufa date missed	187	293
Phase 3
TAK-755	Adam-13 replacement therapy for bleeding disorders	Ph2 Soar-HI data in immune-mediated TTP due 2021; ph3 data in congenital TTP due 2022	265	1,012
TAK-609	Intrathecal formulation of Elaprase for Hunter syndrome	US filing due H2 2021	73	104
Soticlestat (TAK-935)*	Cholesterol 24-hydroxylase inhibitor for rare epilepsies	Ph3 in Lennox-Gastaut syndrome & Dravet syndrome not yet recruiting	59	165
Phase 2
TAK-999 (ARO-AAT)**	Alpha-1 antitrypsin RNAi project	Ph2 Sequoia in alpha-1 antitrypsin deficiency	247	1,739
TAK-994	Orexin 2 receptor agonist for narcolepsy	Ph2 terminated on toxicity signal	389	1,657
TAK-214 (HIL-214)	Norovirus vaccine	Ph2 ongoing; Takeda forming HilleVax, JV with Frazier Healthcare Partners, to commercialise	273	1,004
TAK-007	Anti-CD19 CAR-NK cell therapy	Ph2 in r/r NHL not yet recruiting	266	1,163
TAK-611	Arylsulphatase A stimulant	Ph2 Embolden in metachromatic leukodystrophy	55	184
TAK-607	Growth hormone for complications of prematurity	Pedal in retinopathy & NCT03253263 in lung disease	3	1
TAK-041^	G protein-coupled receptor 139 agonist	Ph2 completed in anhedonia in depression	-	-
TAK-071	Muscarinic M1 receptor positive allosteric regulator	Ph2 in Parkinson's	-	-
TAK-186 (MVC-101)	T-cell engager	Ph1/2 in solid tumours	-	-
TAK-981	Sumo inhibitor	Ph1/2 in various cancers including NHL	-	-
Mezagitamab (TAK-079)^^	Lymphocyte differentiation antigen CD38 antibody	Ph2 in immune thrombocytopenia & myasthenia gravis	-	-
Sibofimloc (TAK-018/EB8018)	Bacterial fimbrial adhesin inhibitor	Ph2 in Crohn's	-	-
TAK-101	Gliadin desensitiser	Ph2 in coeliac disease	-	-
TAK-906	Dopamine D2 & D3 receptor antagonist	Ph2 completed in gastroparesis	-	-
TAK-951	Peptide agonist	Ph2 in post-operative nausea & vomiting	-	-
TAK-954	5-HT4 receptor agonist	Ph2 in postoperative gastrointestinal dysfunction	-	-
*Licensed from Ovid; **Partnered with Arrowhead & sales attributed to Arrowhead; ^Partnered with Neurocrine; ^Partnered with Xoma. Source: Evaluate Pharma & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/trial-results/takeda-gets-pipeline-blues

Curative Biotech Acquires License to Develop Proprietary Next-Gen COVID-19 Vaccine

 Curative Biotechnology, Inc. (OTC: CUBT) ("Curative Biotech" or the "Company") announced today that the Company has reached agreement with Mid-Atlantic BioTherapeutics (MABT) to broaden its previously announced license of IMT504, a novel patented immunotherapy and adjuvant, to include the development of a next generation COVID-19 vaccine. The Company will initially develop the vaccine to address the kidney failure patient population. This new license, utilizing IMT504 as an adjuvant on top of a proprietary protein vaccine, adds a second infectious disease program to the Curative Biotech product development portfolio which also includes a reformulation of Metformin licensed from the National Eye Institute at National Institutes of Health (NIH) to treat degenerative eye diseases; and a novel monoclonal antibody/drug combination to treat brain cancer licensed from the National Cancer Institute at NIH.

"It is becoming increasingly clear that the initial COVID-19 vaccines developed are not working for everyone. There are highly vulnerable people, such as those patients with kidney failure who require kidney transplantation or dialysis, who are being left behind. We need targeted vaccines for this immunocompromised patient group," said Curative Biotech Chairman & President Paul Michaels.

Curative Biotech and Mid-Atlantic BioTherapeutics have agreed to develop a next generation COVID-19 vaccine targeted to meet the needs of this vulnerable population. A consequence of kidney failure in general is the loss of a robust immunologic response to infections, including COVID-19. This means that kidney failure patients may get a more severe version of COVID-19 that could lead to a greater chance of hospitalization or even death. 

https://www.prnewswire.com/news-releases/curative-biotechnology-announces-imt504-license-for-development-of-proprietary-next-gen-covid-19-vaccine-301395252.html

Merus Presents Strong Early Data on Anti-Cancer Agents

 

• Tumor shrinkage and partial responses observed in patients with advanced head and neck squamous cell carcinoma (HNSCC) treated with MCLA-158

• In preclinical studies, Zeno observed to block cell growth 100 fold more potently than anti-HER3 antibody alone

 Merus N.V. (Nasdaq: MRUS) (“Merus”, “the Company”, “we”, or “our”), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics® and Triclonics®), today presented clinical data on MCLA-158, including clinical responses observed in advanced head and neck squamous cell carcinoma (HNSCC) and preclinical data on zenocutuzumab (Zeno) at the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics.

Dr. Andrew Joe, Chief Medical Officer at Merus, said, “We are encouraged by the early evidence of clinical activity of MCLA-158 in patients with advanced, previously treated HNSCC, further validating the potential of our Biclonics® platform. With Zeno, our preclinical research continues to reinforce the mechanisms by which Zeno is capable of potently inhibiting the growth of NRG1 fusion cancers.”

https://finance.yahoo.com/news/merus-presents-early-clinical-data-130000593.html

Y-mAbs cancer treatment gets rare pediatric disease tag

 Y-mAbs Therapeutics, Inc. (“Y-mAbs” or the “Company”) (NASDAQ: YMAB), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, today announced that the U.S. Food and Drug Administration (“FDA”) has granted Rare Pediatric Disease Designation (“RPDD”) for the Company’s lutetium labelled omburtamab antibody program for the treatment of medulloblastoma.

177Lu-omburtamab-DTPA, a monoclonal B7-H3 antibody that has been radiolabeled with lutetium-177, is currently in a multicenter Phase 1 clinical trial in pediatric patients with refractory medulloblastoma, and in a multicenter Phase 1 clinical trial targeting B7-H3 positive CNS/LM tumors in adults. We believe that both indications address clear unmet medical needs.

https://finance.yahoo.com/news/y-mabs-177lu-omburtamab-dtpa-130000607.html

Voyager upped to Outperform from Neutral by Baird

 Target to $9 from $6

https://finviz.com/quote.ashx?t=VYGR

Ginkgo Bioworks 'a hoax for the ages,' says activist short seller firm

 Calling its business model “hocus-pocus” and “a colossal scam,” activist short seller firm Scorpion Capital has stung Ginkgo Bioworks. The synthetic biology company went public less than a month ago through a $1.6 billion special purpose acquisition company deal, which bestowed upon it a $23 billion market cap.

Though it has promised the ability to harness living organisms to produce a range of industrial and biopharmaceutical chemicals through genetic editing, Scorpion said Ginkgo’s methods differ little from decades-old practices used to engineer yeast strains to manufacture food flavorings, fragrances, drug ingredients and more.

In addition, the short seller said the majority of the company’s current income is based on “a dubious shell game” made up of customers that Ginkgo itself helped create and invested in, sending its money on a round-trip journey back into Ginkgo’s accounts.

In about an hour following the publication of Scorpion’s 175-page report, Ginkgo’s stock price dropped at least 20%, down to about $9.50 a share. The report includes statements from current and former Ginkgo employees as well as others at connected companies. Ginkgo is currently trading at about $10. The company did not respond to requests for comment.

“Based on interviews with its related-party ‘customers,’ we believe that at least half of Ginkgo’s reported foundry revenue is phantom—that is, noncash and pure accounting hocus-pocus,” Scorpion wrote in its report, calling it a "hoax for the ages."

The firm said it spoke with a senior member of one of Ginkgo’s largest customers, linked to tens of millions of dollars in reported deferred revenue, who said it never paid Ginkgo cash for its R&D services and instead used “free credits” that were given following equity investments by Ginkgo and Viking Global Investors, one of Ginkgo’s largest backers.

Ginkgo’s share price drop is another recent stumble for self-described synthetic biology companies: This past summer, Zymergen watched its stock drop by as much as 75% in one day after it disclosed severe setbacks in its commercial pipeline plus the departure of its CEO.

Like Ginkgo, Zymergen raised hundreds of millions with the promise of enlisting genetically engineered microbes to assemble materials from the molecule up for buyers in the electronics, agriculture and healthcare industries. That includes a thin, transparent film that the company hopes will serve as its lead product in electronic touchscreens and foldable smartphones—but one that has run into trouble as customers try to incorporate it into their tech products, erasing the company’s expectations of substantial revenue through next year.

The news came just months after Zymergen went public through a $500 million IPO. Co-founder Josh Hoffman stepped down as chief, while former Illumina CEO Jay Flatley was tapped to serve as acting CEO.

Ginkgo, meanwhile, claimed the surprisingly available NYSE ticker “DNA” through a SPAC deal announced this past May, backed by Soaring Eagle Acquisition Corp. and Bellco Capital, the venture firm led by ex-Kite Pharma CEO Arie Belldegrun, M.D., who also joined Ginkgo’s board of directors.

https://www.fiercebiotech.com/medtech/ginkgo-bioworks-suffers-short-attack-firm-calling-it-a-hoax-for-ages