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.

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Novartis (NVS) made headlines worldwide when it disclosed—via email statement to GEN and other news outlets—that it will eliminate about 8,000 jobs worldwide. About 18% of those jobs (1,400) are in Novartis’ headquarters country of Switzerland, where the company is based in Basel (The company has not broken out job reductions planned for other countries, including the U.S.).

The job reduction amounts to 7% of the pharma giant’s global workforce of 108,000, yet investors appeared to be hardly fazed by the layoff news. After a 1% dip in the price of its shares (traded in Zurich on the SIX Swiss Exchange) and its American Depositary Shares (ADSs, traded on the New York Stock Exchange), Novartis rebounded on Wednesday with under 1% gains for its shares, which rose up 0.06% to CHF 81.19  ($84.97) and 0.7% for its ADSs, up to $84.77.

But the rebound ended by Thursday as Novartis shares and ADSs dipped under 1% again, to CHF 80.65 ($84.40) and $84.54, respectively.

One likely reason why Novartis’ stock didn’t tank was because investors had come to expect the magnitude of the layoffs—part of a global restructuring that is intended to save the pharma giant at least $1 billion by 2024.

When the outlines of the restructuring were first announced by Novartis in April, CEO Vas Narasimhan quantified the expected job loss by saying it would be “a number in the single-digit thousands.” Those outlines included job reductions Novartis said back then would reach “a number in the single-digit thousands,” as well as a goal of delivering at least 4% annual sales growth through 2026, and a combining of its pharmaceuticals and oncology business units.

Another likely reason for investors staying sanguine about Novartis can be found in a commentary published last week by Morningstar analysts Karen Andersen and Damien Conover. They observed that Novartis was laying the foundation for steady long-term growth once it gets past short-term challenges—namely the loss of patent exclusivity on its anemia drug Exjade and cancer drug Afinitor.

That foundation, they wrote, includes several multi-billion-dollar blockbuster drugs—led by Cosentyx® (secukinumab), whose numerous indications include Psoriasis, ankylosing spondylitis, psoriatic arthritis, and non-radiographic axial spondyloarthritis. Last year Cosentyx led Novartis’ marketed products with net sales of $4.718 billion (up 18% from 2020) and $1.159 billion in the first quarter of this year (up 12% from Q1 2021). Novartis’ number-two marketed drug, Entresto® (Sacubitril/valsartan), indicated for chronic heart failure, racked up $3.548 billion (up 42% year-over-year) and $1.093 billion in Q1 2022 (up another 42% YoY).

Also part of Novartis’ foundation for long-term growth, Andersen and Conover added, are:

  • Its pipeline of more than 150 programs, of which 52 are in Phase III, according to the company’s website.
  • Spinoffs of some operations; Novartis generated $20.7 billion last year by selling off a 33% share in rival Swiss pharma giant Roche. But Novartis is still exploring whether it will spin off its Sandoz generic drug unit, a move also expected to generate billions.

“Novartis’ strategy to focus largely in areas of unmet medical need should strengthen the firm’s pricing power,” the Morningstar analysts wrote. “The combination of a strong pipeline of new products and a diverse, well-positioned operating platform should translate into steady growth.”

Agenus (AGEN)

Agenus shares surged 31.5% to $2.4197 a share on Wednesday morning before ending the day at $2.04, 11% above Tuesday’s close. The surge followed Agenus announcing positive “unprecedented activity” in a Phase Ib trial assessing its combination of botensilimab (Fc-enhanced anti-CTLA-4) and balstilimab (anti-PD-1) in patients with microsatellite stable colorectal cancer (MSS CRC).

Out of 41 evaluable patients, the combination showed a 73% “disease control” rate (defined as partial response and stable disease patients), a 50% objective response rate with greater than 50% tumor reduction—although the patient population’s overall response rate was just 24%. At the point of data cutoff, the objective response rate was 80%. The rate of objective responses exceeding one year was 30%.

And in a key patient subpopulation—five patients with RAS mutations—the combination showed a 24% overall response rate and 81% disease control rate—better outcomes that the ≤1% response rate Agenus said had been shown by other PD-1 combinations in clinical trials.

The standard of care offers only a 1-2% response rate and a median expected survival ranging from 6 to 7 months, the company said in a statement attributed to the director of the combination’s Phase I program, Anthony El-Khoueiry, MD, of the USC Norris Comprehensive Cancer Center, Keck Medicine of USC.

“Thus far, botensilimab has demonstrated activity in nine cold and treatment-resistant cancers [MSS CRC is a cold tumor], and we plan to initiate a robust, global Phase II program, including in MSS CRC, later this year,” stated Agenus chief medical officer Steven O’Day, MD.

Aileron Therapeutics (ALRN)

Shares of Aileron Therapeutics stumbled 35% between Wednesday and Thursday, from 40 cents to 26 cents a share, after the company said it would halt further enrollment in its Phase Ib chemoprotection trial (NCT04022876) evaluating its sole clinical candidate ALRN-6924 in Patients with p53-mutated non-small cell lung cancer (NSCLC).

Following an interim analysis of the study’s first 20 patients, Aileron said patients on ALRN-6924 were able to stay on treatment longer, completing more of the first four cycles of the chemotherapy combination of carboplatin and pemetrexed (93% of cycles on ALRN-6924 versus 78% on placebo). The gap widened among patients completing six cycles (79% on ALRN-6924 vs. 57% on placebo).

“The more cycles patients completed the more opportunity they had to experience toxicities. This introduced an imbalance of toxicities between the active and placebo arms and, may have resulted in a bias against ALRN-6924 on the composite primary endpoint,” Manuel Aivado, MD, PhD, Aileron’s President and CEO, said in a statement.

The composite primary endpoint consisted of the proportion of treatment cycles free of Grade ≥3 neutropenia, Grade ≥3 thrombocytopenia, Grade ≥3 anemia, blood transfusions, and the use of growth factors, as well as dose reductions or dose delays within the first 4 cycles of treatment.

Angion Biomedica (ANGN)

Angion shares plummeted 40% this week, mostly due to a 33% plunge on Thursday from $1.71 to $1.14 after the company said it was ending its Phase II JUNIPER trial (NCT04939116) assessing its sole pipeline clinical-phase candidate ANG-3070 in patients with primary proteinuric kidney diseases, specifically focal segmental glomerulosclerosis (FSGS) and immunoglobulin A nephropathy (IgAN).

President and CEO Jay Venkatesan said in a statement that his company would “consider all strategic and operational options for Angion and its pipeline going forward.” He also said Angion will “deprioritize” ANG-3070 in established, serious kidney disease, and continue studying the oral tyrosine kinase inhibitor (TKI) in idiopathic pulmonary fibrosis, for which Angion has a Phase I trial (NCT05387785) that has yet to recruit patients.

The company cited patient safety in ending the kidney disease trial, specifically an “unexpected and substantial” decline in kidney function in a patient in the trial’s drug treatment arm. The decline was not further explained or quantified in a press release announcing the trial halt.

That led to a reassessment of ANG-3070’s risk/benefit profile in patients with established serious kidney disease, Angion said. The company’s review of the safety signal included a number of factors, including TKI class side effects, including potential adverse effects on the kidney; and an analysis of blinded patient data, which according to the company did not detect any early treatment signal indicating a reduction in proteinuria.

NeuroSense Therapeutics (NRSN)

NeuroSense Therapeutics shares nearly doubled this week, rocketing 94% following two surges, a 47% leap on Monday (from $1.70 to $2.50) and a 23% jump on Thursday (from 2.74 to 3.38).

The company delivered a pair of positive announcements, beginning Monday by trumpeting positive preliminary results from Stage III of its biomarker study conducted with Massachusetts General Hospital (MGH) to evaluate PrimeC, NeuroSense’s lead combination drug candidate for the treatment of amyotrophic lateral sclerosis (ALS).

NeuroSense said patients treated with PrimeC showed a statistically significant decline in disease biomarkers—though its announcement didn’t share data, saying more detailed results would be shared at the World Orphan Drug Congress set for July 11-13 in Boston.

PrimeC is designed to fight ALS through triple direct targeting of the deadly neurodegenerative disorder also known as Lou Gehrig’s disease—which entails regulating microRNA synthesis, influencing iron accumulation, and reducing neuroinflammation, all hallmarks of ALS pathologies.

NeuroSense recently enrolled its first patients in its Phase IIb PARADIGM trial  (NCT05357950), assessing PrimeC’s safety, tolerability, and efficacy in people living with ALS. NeuroSense expects to complete enrollment in PARADIGM by year’s end, with topline results set to be reported in the second quarter of 2023.

Three days later on Thursday, NeuroSense announced results from a biomarker study of its Alzheimer’s disease (AD) candidate CogniC showing high levels of transactive response DNA binding protein of 43 kDa (TDP-43) in people who suffer from AD, when compared to the healthy control group. The company cited a 2021 study showing that TDP-43 had been found in up to 57% of AD cases and aggregates of TDP-43 had been shown to be cytotoxic both in vitro and in vivo.

The biomarker study identified several biomarkers associated with AD—such as miRNA dysregulation, lysosomal dysfunction, and impaired autophagy—which according to NeuroSense indicated that CogniC’s mechanism of action may be effective in targeting the pathways involved in the disease. Among the biomarkers, hallmarks of AD were also detected, such as increased levels of amyloid-β (Aβ) and intracellular aggregates of tau protein.

“Having identified these promising biomarkers, which have the potential to be modulated by CogniC, we are now preparing to carry out a clinical proof-of-concept study in conjunction with a leading AD clinic,” stated NeuroSense CEO, Alon Ben-Noon.

That study is expected to begin in 2023.