Stay at the forefront of the week’s champions and runners-up among publicly traded biotech companies and the reasons behind the ups or downs of their stock price fluctuations.
Biogen (BIIB)’s second cost-cutting restructuring in five months—which includes the planned exit of CEO Michel Vounatsos after six years—hardly raised an eyebrow with investors, as the company’s shares stayed relatively flat this week.
In announcing first-quarter results on Tuesday, Biogen said it had begun searching for a successor to Vounatsos, who will remain in his position until the new CEO’s appointment takes effect. The company’s announcement offered no reason for the CEO transition, though Vounatsos’ tenure has been marked by Biogen’s advancement of the controversial yet approved Alzheimer’s disease drug Aduhelm (aducanumab-avwa).
Biogen and Eisai co-developed the drug. But in March, Biogen obtained sole decision-making authority over the development, commercialization and manufacturing of Aduhelm when Eisai gave up sharing global profits in favor of a global royalty arrangement starting at 2% and reaching 8% when annual sales exceed $1 billion. Two days later, Biogen trumpeted positive 128-week data that lifted shares 8%.
Last month, the Centers for Medicare and Medicaid Services (CMS) issued a National Coverage Determination limiting coverage of that and other amyloid-beta targeting Alzheimer’s disease therapies receiving accelerated approval to those in FDA- of NIH-approved clinical trials. “This unprecedented CMS decision effectively denies all Medicare beneficiaries access to Aduhelm,” Vounatsos fumed.
Biogen blamed the restrictions for its decision to “substantially” eliminate its commercial infrastructure supporting Aduhelm. The company added that it would retain “minimal” resources to manage patient access programs, including a continued free drug program for patients currently being treated with Aduhelm in the U.S. Biogen said it will take $38 million in charges primarily associated with its global commercial infrastructure supporting Aduhelm.
Still to be funded, Biogen added, are regulatory and R&D activities connected with Aduhelm, including the continuation of the Phase III EMBARK re-dosing trial (NCT04241068) and the launch of the Phase IV post-marketing ENVISION trial (NCT05310071) required as a condition of approval.
Aduhelm generated sales of only $2.8 million in the first quarter. Biogen said it will incur another approximately $275 million of charges from writing off the value of Aduhelm inventory.
The cutbacks for Aduhelm are part of a restructuring intended to save Biogen $500 million a year—on top of the $500 million in savings the company projected from a restructuring it launched in December 2021.
Investors initially responded to the Q1 results, Vounatsos exit, and Aduhelm news by sending shares down 0.8% on Tuesday, to $205.70 from $207.32 at the close on Monday. Investors yo-yoed back to Biogen on Wednesday, sending shares up 2% to $210.10, before shares fell 4% Thursday to $201.18.
“It was a busy day of earnings, and investors probably need time to ‘run the numbers’ and think about ‘what ifs’ to determine if this is in fact a good value investment. It certainly seems that way to us, but we admit that patience will be needed,” Marc Goodman, a Senior Research Analyst at SVB Securities covering Neuroscience and Ophthalmology, wrote Tuesday in a research note.
While execution and implementation of a sizable restructuring program can be challenging, this is the easy decision of the two,” Goodman added.
The harder decision, he added, is what direction should Biogen take its R&D strategy?
“Neuroscience is higher up on the risk curve than most biopharma therapeutics areas, so how far outside of CNS will the company take its franchise? Is it time to add an additional strategic vertical area of focus?” Goodman asked. “Within CNS, it probably makes sense to diversify further into psychiatry at the expense of neurology and the much-needed innovation in neurodegeneration in order to move lower across the development risk curve.”
Connect Biopharma (CNTB)
Shares of Connect plunged 58% on Wednesday, to 82 cents from $1.94 a share, then dropped another 15% to 70 cents a share, after acknowledging that its Th1 cell modulator CBP-307, a small molecule targeting S1P1, failed the Phase II CBP-307CN002 trial (NCT04700449) since while the drug showed a numerical reduction for the primary endpoint of least squares (LS) mean change from baseline in adapted Mayo Score at Week 12, the data did not reach statistical significance.
Connect said it intends to engage in partnership discussions for future development of CBP-307, in order to shift its attention to its lead program, the Phase III-bound CBP-201, a Th2 cell modulator antibody targeting the IL-4Rα cytokine receptor, which is being developed for asthma and atopic dermatitis (where a pivotal trial in that indication is ongoing in China).
Connect—a U.S./China drug developer known there as Suzhou Connect—was quick to add that a significantly higher proportion of patients who received CBP-307 0.2 mg dose achieved clinical remission based on both the complete and adapted Mayo Scores, which has been accepted by the FDA as the primary endpoint in clinical trials supporting earlier approvals for UC treatments. The company also cited reductions in lymphocyte counts among patients with active UC who received CBP-307, 0.2 mg—a confirmation, Connect said, of the drug’s pharmacodynamic activity.
“The overall 12-week results for CBP-307 demonstrate the therapeutic potential to induce a significant treatment response consistent with clinical data of other S1P modulators in patients with UC,” said David T. Rubin, MD, Professor of Medicine and Chief of the Section of Gastroenterology, Hepatology, and Nutrition at The University of Chicago Medicine, in a company statement.
Kymera Therapeutics (KYMR)
Kymera shares tumbled 29% on Tuesday, reaching its 52-week low of $23.17, before ending trading down 24% after the company said it would extend, from 14 days to 28 days, the dosing period for patients in a Phase I trial (NCT04772885) of its lead candidate, the IRAK4 degrader KT-474, in atopic dermatitis (AD) and hidradenitis suppurativa (HS). In addition to those two diseases, KT-474 is designed to treat rheumatoid arthritis and other interleukin-1 receptor (IL-1R)/toll-like receptor (TLR)-driven immune-inflammatory diseases.
The extended dosing period, amended in agreement with the FDA and collaboration partner Sanofi, “will allow for the exploration of clinical endpoints in both HS and AD patients, as well as an extended safety dataset”—namely pharmacokinetics (PK) and pharmacodynamics (PD) data, including key inflammatory biomarker readouts in both skin and plasma,” Kymera stated.
The clinical endpoints to be evaluated include Eczema Area and Severity Index (EASI) for AD, total abscess and inflammatory nodule count for HS, as well as additional measures of symptoms and physician or investigator global assessments for both diseases, Kymera said.
Kymera and Sanofi now say they plan to present clinical data from HS and AD patients to Sanofi for a decision to proceed to Phase II in the second half of this year
In a statement, Kymera Co-Founder, President, and CEO Nello Mainofi, PhD, cited other anticipated pipeline milestones for the company during 2022. These include initial safety and proof-of-mechanism data for Kymera’s two oncology programs, KT-413 and KT-333, and filing an IND for its MDM2 program, KT-253, in the second half of this year.
Shares continued to drop this week, finishing Thursday down another 19.5%, to $20.02.
Sesen Bio (SESN)
Sesen Bio shares jumped 47% this week after the company announced Tuesday that it was exploring strategic alternatives “with the goal of maximizing shareholder value.” The developer of targeted fusion protein therapeutics for treating cancer disclosed that it would explore and evaluate options that included a sale of Sesen, a merger, acquisition or other business combination, a strategic partnership with one or more entities, or the licensing, sale or divestiture of some of the company’s proprietary technologies.
Sesen President and CEO Thomas Cannell, DVM, said in a statement that Sesen will continue its development of Vicineum as a treatment for non-muscle invasive bladder cancer. Cannell said Sesen will seek a meeting with the FDA “in the coming weeks” to discuss outstanding items related to an additional Phase III clinical trial.
“Our strong cash position provides us the opportunity to carefully consider a wide range of potential strategic alternatives designed to maximize shareholder value,” Cannell added.
Sesen said it ended the first quarter with a preliminary $169.8 million in cash and cash equivalents—a figure that could be updated when the company reports Q1 results—as well as no outstanding debt and fewer than 0.2 million outstanding warrants.
Spero Therapeutics (SPRO)
Shares of Spero Therapeutics plunged 71%, from $5.09 to $1.50, at the start of trading Tuesday before ending the day falling 64% to $1.85 after the company that morning announced a “new strategic direction.” That new direction will in part entail eliminating about 75% of Spero’s workforce—approximately 110 jobs, based on the 146 reported at year’s end in its Form 10-K annual report. The restructuring is designed to cut costs and shift resources toward advancing two pipeline candidates, SPR720 and SPR206.
The restructuring will also refocus Spero away from its lead candidate undergoing FDA review, the oral carbapenem-class antibiotic tebipenem HBr. Spero acknowledged Tuesday that the FDA suggested to company executives that its data for tebipenem HBr “may be insufficient to support approval during this review cycle.”
However, Spero added that it remains in talks with the FDA on a regulatory path forward for tebipenem HBr, which if approved would be the first oral carbapenem antibiotic indicated in complicated urinary tract infection and acute pyelonephritis.
SPR720 is an oral antimicrobial agent being developed for the treatment of non-tuberculous mycobacterial (NTM) lung disease. SPR206 is a direct acting intravenous (IV)-administered next-generation polymyxin analogue being developed to treat MDR Gram-negative bacterial infections within the hospital.