This Week in Biotech #32
Catch up on the latest biotech breakthroughs and upcoming trends (Dec 6-12).
Happy December and welcome to This Week in Biotech by Biotech Blueprint!
THIS WEEK’S KEY TAKEAWAYS 🔑
December has brought turbulence to the pharmaceutical landscape, with biotech and pharma companies often delivering significant clinical trial updates toward the year’s end. This week has been dominated entirely by such updates, including both successes and setbacks.
On the extreme ends of the spectrum, uniQure’s Huntington’s disease gene therapy gained potential FDA fast-track designation, driving its stock up by an astounding 150%. In contrast, Keros Therapeutics saw its stock tumble 70% following safety concerns in a pulmonary hypertension trial, while AnaptysBio’s atopic dermatitis treatment failed to meet critical endpoints, resulting in a 30% drop.
In other developments, a retrospective study presented at the American Society of Hematology conference this week analyzed data from over half a million Americans and revealed that GLP-1 drugs significantly reduce the risk of blood clots.
Hope you enjoy this week’s edition. Thanks for reading!
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MARKET UPDATES
🔹 On Dec. 12, Keros Therapeutics’ (KROS) stock plunged over 70% after announcing the voluntary halting of dosing in the 3.0 mg/kg and 4.5 mg/kg treatment arms of its phase 2 TROPOS trial for cibotercept (KER-012) in patients with pulmonary arterial hypertension due to unanticipated pericardial effusion adverse events. Dosing in the 1.5 mg/kg arm continues after a risk-benefit assessment by an independent data monitoring committee. The trial remains fully enrolled, with safety and efficacy data collection ongoing across all arms. Keros plans to present topline data in Q2 2025 and is working with regulatory authorities, including the FDA, to address the safety concerns while prioritizing patient safety.
🔹 On Dec. 11, AnaptysBio (ANAB) announced that its phase 2b trial of ANB032, a BTLA agonist, did not meet its primary or secondary endpoints in treating moderate-to-severe atopic dermatitis. Despite being well-tolerated with no safety issues, ANB032 did not achieve the expected improvements. As a result, AnaptysBio will discontinue further investment in this asset. The company will focus on its other autoimmune therapies, including rosnilimab, a PD-1+ T cell depleter, with phase 2b data for rheumatoid arthritis expected in February 2025. AnaptysBio stock fell over 30% following the announcement.
🔹 On Dec. 11, ADC Therapeutics (ADCT) announced promising initial results from the phase 1b LOTIS-7 trial, which evaluates Zynlonta (loncastuximab tesirine-lpyl) in combination with glofitamab (Columvi) for relapsed or refractory diffuse large B-cell lymphoma. The combination demonstrated a high overall response rate of 94% and a complete response rate of 72%. Safety data indicated a tolerable profile, with no dose-limiting toxicities or severe cases of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). Encouraged by the results, ADC Therapeutics aims to complete dose expansion enrollment in 2025 and engage with regulators on the next steps. The presence of ICANS cases possibly impacted investor sentiment since the stock fell over 35% since the announcement.
🔹 On Dec. 11, Candel Therapeutics (CADL) announced that its investigational viral immunotherapy, CAN-2409, achieved the primary endpoint in a phase 3 clinical trial for intermediate-to-high-risk localized prostate cancer, showing a statistically significant improvement in disease-free survival when combined with radiation therapy compared to radiation alone. CAN-2409, an off-the-shelf adenovirus delivering the HSV-t k gene to tumor cells, is designed to induce a CD8+ T cell-mediated immune response, enhancing the efficacy of local radiotherapy. Following the announcement, Candel’s stock surged nearly 75%.
🔹 On Dec. 10, Q32 Bio (QTTB) announced updates on its bempikibart development program, reporting encouraging clinical activity in alopecia areata but mixed results in atopic dermatitis. In the SIGNAL-AA phase 2a trial, bempikibart showed a meaningful reduction in alopecia hair loss “SALT” scores. However, the trial did not meet its primary endpoint in part B of the study. Q32 Bio’s stock has plummeted ~75%, reflecting investor concerns over mixed clinical results and strategic adjustments.
🔹 uniQure (QURE) has announced a significant milestone in the development of AMT-130, a gene therapy for Huntington’s disease, by reaching an agreement with the FDA on key elements of an accelerated approval pathway. The FDA agreed that data from phase 1/2 studies, compared to a natural history external control, could support a Biologics License Application for accelerated approval without requiring additional pre-approval studies. Interim data from 2024 showed dose-dependent slowing of disease progression and reductions in neurofilament light chain levels. The stock went up over 150% following the news.
🔹 Acelyrin’s (SLRN) stock fell 18% after announcing that its phase 2b/3 clinical trial of izokibep for non-infectious, non-anterior uveitis did not meet its primary endpoint of improving time to treatment failure compared to placebo, nor did it achieve statistical significance for any secondary endpoints. As a result, the company will discontinue further internal investment in izokibep. Acelyrin will focus on its late-stage development of lonigutamab for thyroid eye disease, with the phase 3 program scheduled to start in Q1 2025.
🔹 On Dec. 10, CervoMed’s (CRVO) stock crashed 80% after the company announced topline results from its RewinD-LB phase 2b clinical trial evaluating neflamapimod for dementia. The trial did not meet its primary or secondary endpoints, showing no statistically significant improvements compared to placebo. Analysis revealed that target plasma drug concentrations were not achieved during the trial, potentially affecting outcomes. The company plans to investigate the reasons for the lower plasma concentrations and analyze data from the trial’s open-label extension phase, expected in 2025, to assess the drug’s future development. Neflamapimod, an orally administered drug targeting synaptic dysfunction, showed promise in earlier trials and remains under evaluation for its potential to treat dementia.
🔹 On Dec. 9, Innate Pharma (IPHA) presented data at ASH 2024 showing that lacutamab significantly improved quality of life for patients with advanced cutaneous T-cell lymphoma (CTCL) in the TELLOMAK phase 2 study. The drug reduced severe itching and skin symptoms in Sézary syndrome and mycosis fungoides, with sustained improvements observed from week 5. Translational analysis confirmed its ability to target KIR3DL2-expressing tumor cells, reinforcing its potential as a treatment for CTCL. Following the announcement, Innate Pharma’s stock rose by nearly 30%.
🔹 On Dec. 8, Agios Pharmaceuticals (AGIO) reported positive phase 3 ENERGIZE-T trial results for mitapivat (Pyrukynd) in transfusion-dependent alpha- and beta-thalassemia at the ASH 2024 conference. The study demonstrated significant efficacy, achieving primary and key secondary endpoints, including reductions in transfusion burden and improvements in hemoglobin levels. Regulatory filings for mitapivat were submitted in multiple regions, including the U.S. and European Union. The most frequent adverse effects occurred in at least 10% of patients on mitapivat and included headache, upper respiratory tract infection, initial insomnia, diarrhea and fatigue. Serious treatment-emergent adverse events were reported in 11.0%. The company’s stock dropped by 21%.
BIOTECH NEWS
🔹 Eli Lilly has partnered with the telehealth platform Ro to expand access to its weight loss drug, Zepbound, through its direct-to-consumer platform, LillyDirect. Ro becomes the first platform to integrate with LillyDirect, providing affordable access to Zepbound’s single-dose vials, which were launched to address production shortages of auto-injectors. This move aims to compete with compounded versions of Lilly’s drugs, which have been popular during the shortages, while addressing FDA-approved treatment availability.
CLINICAL TRIAL UPDATES
🔹 Eli Lilly’s phase 3 EMBER-3 study highlights the promising potential of imlunestrant, an investigational oral selective estrogen receptor degrader (SERD), for treating specific type of advanced breast cancer. The study demonstrated significant progression-free survival benefits, reducing the risk of disease progression or death by 38% as monotherapy compared to standard endocrine therapy in patients with ESR1 mutations. When combined with Verzenio (abemaciclib), imlunestrant further reduced this risk by 43% in all patients, regardless of ESR1 mutation status. The results, published in The New England Journal of Medicine and presented at the 2024 San Antonio Breast Cancer Symposium. The study enrolled 874 participants, stratified based on prior therapies, and the safety profile was in line with expectations.
🔹 On Dec. 11, Relay Therapeutics announced updated interim data for RLY-2608, PI3Kα inhibitor, in combination with fulvestrant, showing a median progression-free survival of 11.4 months in second-line patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer. The study demonstrated a 39% confirmed overall response rate across all patients, with a higher 67% overall response rate in those with kinase mutations. Additionally, the safety profile showed manageable and reversible low-grade adverse events, allowing for a 94% median dose intensity. Full phase 1/2 data will be disclosed in 2025.
🔹 On Dec. 9, AbbVie announced positive results from the phase 3 TEMPO-2 trial, which evaluated the investigational drug tavapadon as a flexible-dose monotherapy for Parkinson’s disease. Tavapadon, a D1/D5 partial agonist, significantly improved the combined MDS-UPDRS Parts II and III score and showed a clinically meaningful reduction in the MDS-UPDRS Part II score compared to placebo. AbbVie plans to submit a New Drug Application to the FDA in 2025. The trial’s safety profile was consistent with previous studies, with mild to moderate adverse events. The TEMPO clinical development program includes multiple trials assessing tavapadon’s efficacy, safety, and tolerability.
🔹 On Dec. 9, Affimed reported encouraging phase 1 data for AFM28, a bispecific innate cell engager targeting CD123 and CD16A, in relapsed/refractory acute myeloid leukemia (r/r AML). At the highest tested dose (300 mg), AFM28 achieved a composite complete remission rate of 40% in heavily pretreated patients, with four patients remaining on treatment. The study included 29 patients with adverse risk profiles per ELN2022 guidelines. AFM28 demonstrated a favorable safety profile, with mild to moderate infusion-related reactions as the most common side effect, and no neurotoxicity or immune-related adverse effects reported. Based on the results, further evaluation at higher doses is planned.
🔹 On Dec. 9, Sellas Life Sciences announced promising data from its phase 2 trial of SLS009, a selective CDK9 inhibitor, for relapsed/refractory acute myeloid leukemia (r/r AML). The trial showed a median overall survival exceeding 7.7 months in patients refractory to venetoclax-based regimens, significantly surpassing the historical survival of 2.5 months. Additionally, an overall response rate of 56% was observed in patients with AML and myelodysplasia-related changes (AML-MRC), exceeding the pre-specified target of 33%. SLS009 was well-tolerated, with no new safety signals reported.
🔹 On Dec. 7, Incyte announced positive results from the phase 3 POD1UM-304 trial of retifanlimab (Zynyz) in combination with platinum-based chemotherapy for the treatment of adults with previously untreated metastatic non-small cell lung cancer (NSCLC). The trial met its primary endpoint of overall survival, with patients in the retifanlimab group experiencing a median overall survival of 18.1 months compared to 13.4 months in the placebo group. The treatment was generally well-tolerated, with no new safety concerns identified. Incyte plans to submit a supplemental Biologics License Application for retifanlimab in NSCLC to the FDA in 2025.
PUBLIC HEALTH SPOTLIGHT
🔹 A new study suggests that GLP-1 diabetes medications, such as Ozempic and Mounjaro, may reduce the risk of venous thromboembolism (VTE), a dangerous type of blood clot, by 20% compared to older diabetes drugs like DPP4 inhibitors. The research, presented at the American Society of Hematology meeting, analyzed data from over 558,000 U.S. patients, showing fewer VTE incidents, including pulmonary embolisms and deep vein thromboses, among those using GLP-1 drugs. Notably, the benefit was consistent regardless of patients’ obesity status, although the mechanism, whether due to weight loss or other factors, remains unclear. While the retrospective nature of the study preve
nts confirmation of causation, the findings suggest GLP-1 drugs could influence treatment decisions, particularly for patients at increased clotting risk.
ON THE HORIZON
🔹 Dec. 2024 FDA PDUFAs:
Dec. 19: Olezarsen, an investigational RNA-targeted medicine developed by Ionis Pharmaceuticals, is designed to treat familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (sHTG) by lowering triglyceride levels. It is currently under Priority Review by the FDA for the treatment of FCS, with a decision expected by Dec. 19, 2024. Olezarsen works by targeting apoC-III, a protein involved in triglyceride metabolism, and aims to reduce the risk of life-threatening acute pancreatitis and other complications related to these conditions.
Dec. 20: In Feb. 2024 AstraZeneca and Daiichi Sankyo’s Biologics License Application for datopotamab deruxtecan was accepted in the U.S. for treating patients with previously treated advanced nonsquamous non-small cell lung cancer, based on promising results from the TROPION-Lung01 phase 3 trial. If approved, it could become the first TROP2-directed antibody drug conjugate for lung cancer treatment.
Dec. 22: Glepaglutide by Zealand Pharma is a long-acting GLP-2 analog developed for the treatment of adult patients with short bowel syndrome (SBS) who are dependent on parenteral support, aiming to reduce or eliminate the need for such support and improve patients’ quality of life.
Dec. 27: DCCR (Diazoxide Choline) Extended-Release Tablets are being developed by Soleno Therapeutics for the treatment of hyperphagia, a life-threatening symptom of Prader-Willi Syndrome (PWS), in individuals aged four and older. The drug aims to address the excessive hunger and food-seeking behaviors that significantly impact the quality of life for those with PWS.
Dec. 28: Chenodiol is being developed by Mirum Pharmaceuticals as a treatment for cerebrotendinous xanthomatosis (CTX), a rare genetic disorder that affects cholesterol metabolism. In CTX, bile alcohols and cholestanol build up in the body, leading to symptoms such as chronic diarrhea, cataracts, tendon xanthomas, and neurological deterioration. Chenodiol works by reducing these toxic substances and is potentially the first approved therapy for CTX in the U.S. The FDA submission is based on the positive results of a phase 3 study, which demonstrated its ability to lower bile alcohols and improve cholestanol levels.
Dec. 28: Ensartinib is a next-generation oral tyrosine kinase inhibitor being developed by Xcovery Holdings for the first-line treatment of patients with metastatic ALK-positive non-small cell lung cancer (NSCLC). It is currently being evaluated in a phase 3 study, where it has shown superior progression-free survival compared to crizotinib. Ensartinib also demonstrated a higher intracranial response rate in patients with brain metastases.
Dec. 28: Cosibelimab is being developed by Checkpoint Therapeutics as a treatment for adults with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who are not eligible for curative surgery or radiotherapy. The drug has shown promising efficacy, with a confirmed objective response rate of 47.4% in a phase 1 trial, and is being reviewed by the FDA for approval.
Dec. 30: Crinecerfont, developed by Neurocrine Biosciences, is an investigational drug aimed at treating congenital adrenal hyperplasia (CAH), a rare endocrine disorder caused by 21-hydroxylase deficiency. It works by reducing excess adrenocorticotropic hormone (ACTH) and adrenal androgens, potentially offering a safer treatment option than current therapies, which rely on supraphysiologic glucocorticoid doses.
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