This Week in Biotech #005
Welcome to This Week in Biotech by Biotech Blueprint, your source for the latest biotech breakthroughs, clinical trial updates, pharma industry news, and expert forecasts on what’s ahead in the world of biotechnology.
MARKET UPDATE
?? Following the WHO’s declaration of mpox as a public health emergency of international concern on August 14, several companies involved in developing vaccines, PCR tests, and antivirals for mpox have seen significant market activity. Shares of Bavarian Nordic (BAVA), Emergent BioSolutions (EBS), GeoVax Labs (GOVX), Applied DNA Sciences (APDN), and Virax Biolabs (VRAX) surged earlier this week, though some have pulled back in the past few days.
Emergent BioSolutions, currently trading at around $10 per share, has committed to donating 50,000 doses of its ACAM2000 vaccine to combat the mpox outbreak in Africa, with a focus on the Democratic Republic of the Congo. The company’s shares had previously peaked at $133.42 in August 2022 during the initial mpox outbreak.
While the rally in biotech stocks related to mpox is notable, it is essential to approach these recent developments with caution. Historical trends indicate that market reactions to health emergencies can be volatile. For instance, after the 2022 mpox outbreak, Bavarian Nordic’s stock also surged but later fell back to pre-outbreak levels by May 2023. Similarly, the recent stock gains of many companies could be fleeting, driven by speculative trading rather than fundamental business advancements.
?? Verrica Pharmaceuticals (VRCA) announced promising preliminary results from part 2 of its phase 2 clinical trial evaluating VP-315, an investigational oncolytic peptide, for treating basal cell carcinoma. The study, involving 92 patients, demonstrated an overall tumor size reduction of approximately 86% across all treated lesions. Notably, 51% of lesions achieved complete histologic clearance with no remaining tumor cells. Despite these results, the stock took a dip of almost 50% since the announcement.
The factors that may have contributed to this unexpected market reaction dip might be because the company’s announcement indicated that genomic and T cell data will not be available until the first quarter of 2025. Investors often prefer immediate clarity on the full scope of a treatment’s efficacy and safety profile.
Additionally, the company plans to request an end-of-phase 2 meeting with the FDA, which introduces an element of uncertainty. Regulatory feedback can significantly alter the development trajectory of a drug, and investors might be wary of potential hurdles that could arise during this process.
?? The FDA granted tentative approval to Liquidia Corporation’s YUTREPIA for pulmonary arterial hypertension, but final approval is delayed until May 2025 due to United Therapeutics’ exclusivity on Tyvaso. Liquidia has filed a lawsuit challenging the FDA’s decision, and its shares have dropped significantly following the news. Yesterday afternoon, Liquidia shares were down 3.5% in one day and almost 32% on a 5-day basis.
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BIOTECH NEWS
?? On August 22, Moderna and Pfizer/BioNTech announced that the FDA approved their updated 2024-2025 COVID-19 vaccines, both adapted to the Omicron KP.2 variant, for individuals aged 12 and older. The vaccines also received Emergency Use Authorization (EUA) for children aged 6 months to 11 years. These vaccines are tailored for the 2024-2025 fall and winter season and will be available in pharmacies, hospitals, and clinics across the U.S. in the coming days.
?? On August 21, Bristol Myers Squibb announced that the FDA accepted its supplemental Biologics License Application for the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) as a potential first-line treatment for adult patients with unresectable hepatocellular carcinoma (HCC). The acceptance is based on phase 3 CheckMate -9DW trial results, which showed that the combination therapy significantly improved overall survival compared to lenvatinib or sorafenib. The FDA has set a target decision date of April 21, 2025. This application could lead to a new first-line treatment option for HCC, the most common form of liver cancer.
?? On August 21, Roche announced that it is actively working to increase laboratory testing capacity for mpox globally. Roche is collaborating with governments, healthcare providers, and organizations to enhance testing capabilities.
?? On August 20, GSK received a Breakthrough Therapy Designation from the FDA for its investigational B7-H3-targeted antibody-drug conjugate, GSK5764227 (GSK’227), for the treatment of relapsed or refractory extensive-stage small-cell lung cancer (ES-SCLC). This designation is based on promising early clinical evidence from the ongoing ARTEMIS-001 phase 1 trial, suggesting that GSK’227 could significantly improve outcomes for patients with this aggressive cancer, which currently has very limited treatment options and poor survival rates. The designation aims to expedite the drug’s development and review, with GSK planning to initiate global phase 1/2 trials in the second half of 2024.
?? On August 20, Aadi Bioscience announced the halt of its phase 2 PRECISION1 trial for Fyarro (nab-sirolimus) in patients with solid tumors due to the trial’s unlikely success in meeting the efficacy needed for accelerated FDA approval. This setback has prompted Aadi to shift its focus towards maximizing its commercial business for Fyarro, which is already approved for treating a rare cancer called perivascular epithelioid cell tumor. Additionally, the company will significantly reduce its R&D workforce by 80% and pause new enrollments in two ongoing phase 2 trials for other cancer indications.
?? On August 20, Regeneron announced that the FDA issued a response for linvoseltamab, a treatment for relapsed/refractory multiple myeloma that has progressed after at least three prior therapies. The only issue identified by the FDA relates to findings from a pre-approval inspection at a third-party manufacturer for another company’s product. Although this issue has been rectified, the third party is awaiting reinspection by the FDA in the coming months. Regeneron CEO Leonard Schleifer emphasized that the FDA has not raised any concerns regarding the safety, efficacy, or ongoing confirmatory trials of linvoseltamab. Meanwhile, the European Medicines Agency (EMA) continues to review linvoseltamab for the same indication.
?? On August 20, the FDA approved Johnson & Johnson’s combination of RYBREVANT (amivantamab-vmjw) and LAZCLUZE (lazertinib) as a first-line treatment for adults with advanced non-small cell lung cancer (NSCLC) that has EGFR mutations. This approval is based on the phase 3 MARIPOSA study, which demonstrated that this regimen is the only chemotherapy-free option showing superior results compared to osimertinib, a current standard treatment. RYBREVANT + LAZCLUZE reduced the risk of disease progression or death by 30% compared to osimertinib. It also offered a nine-month longer median duration of response (25.8 months vs. 16.7 months). The safety profile includes risks such as infusion-related reactions and venous thromboembolic events, but overall, the combination offers a new and effective chemotherapy-free treatment option for EGFR-mutated NSCLC.
?? On August 20, Johnson & Johnson agreed to acquire V-Wave Ltd., a company specializing in heart failure treatments, for $600M upfront with potential additional payments up to $1.1BN. This acquisition, expected to finalize by the end of 2024, will integrate V-Wave’s innovative Ventura Interatrial Shunt (IAS) into Johnson & Johnson MedTech’s cardiovascular portfolio. The Ventura IAS device aims to address heart failure with reduced ejection fraction (HFrEF) by creating a shunt between the left and right atrium to alleviate elevated left atrial pressure. The acquisition is set to enhance Johnson & Johnson’s position in cardiovascular innovation and meet the needs of the estimated 800,000 HFrEF patients in the U.S.
?? On August 19, Emergent BioSolutions pledged to donate 50,000 doses of its smallpox vaccine, ACAM2000, to help combat the mpox outbreak in Africa, particularly in the Democratic Republic of the Congo (DRC) and surrounding countries. This donation, coordinated through Direct Relief, responds to a call for more equitable vaccine distribution following the emergence of a new mpox variant, clade 1b, which has rapidly spread in Africa and reached Sweden (August 15) and Thailand (August 22). The Africa Centres for Disease Control and Prevention (CDC) recently declared a public health emergency, which was followed by a global emergency declaration by the World Health Organization (WHO). Emergent’s donation comes amid a rise in their stock value and follows similar contributions from Bavarian Nordic, which has pledged 40,000 doses of its JYNNEOS vaccine. Bavarian Nordic is also preparing for trials in Africa to test its vaccine in children, potentially expanding its use in younger age groups.
Read more on the recent mpox outbreak:
?? On August 20, Talus Bioscience, a drug discovery company, announced it has secured $11.2M in new funding, led by Two Bear Capital, to advance its AI-driven MARMOT platform. This platform aims to discover and optimize modulators for transcription factors, including those previously considered “undruggable.” The funding will support Talus Bio’s therapeutic programs targeting Brachyury-driven cancers and transcription factors linked to prostate cancer. The company has also secured over $7.3 million in grants and $19.7 million in total venture funding.
?? On August 19, the FDA granted tentative approval to Liquidia Corporation’s YUTREPIA (treprostinil) inhalation powder for treating adults with pulmonary arterial hypertension. The final approval is pending the expiration of United Therapeutics’ Tyvaso exclusivity rights, which limits Liquidia’s ability to fully launch its drug until May 2025. The decision followed positive results from the phase 3 INSPIRE trial, demonstrating YUTREPIA’s safety and efficacy. On August 22, Liquidia filed a lawsuit challenging the FDA’s decision. Yesterday afternoon, Liquidia shares were down 3.51% in one day and almost 32% on a 5-day basis.
?? On August 19, ENHERTU (fam-trastuzumab deruxtecan-nxki), developed by Daiichi Sankyo and AstraZeneca, was granted Breakthrough Therapy Designation (BTD) by the FDA for treating specific cases of HER2 low or HER2 ultralow metastatic breast cancer. This designation is based on promising results from the DESTINY-Breast06 phase 3 trial, which were presented at the 2024 ASCO Annual Meeting. The BTD is meant to expedite the development and review of treatments that address serious conditions with significant unmet needs. ENHERTU, an HER2-targeted antibody drug conjugate, now holds eight BTDs, including for various types of metastatic breast cancer and other HER2-positive cancers.
?? Pfizer has expanded its digital leadership team by appointing Berta Rodriguez-Hervas as Chief AI and Analytics Officer. With a robust background in AI and machine learning from roles at Stellantis, Tesla, and NVIDIA, Rodriguez-Hervas will also co-chair Pfizer’s AI council. Her expertise is expected to enhance Pfizer’s AI strategies, contributing to the development of medicines and vaccines, improving clinical trials, and optimizing internal processes. This appointment reflects a broader industry trend of companies adding specialized AI leadership roles to stay competitive, a shift seen across sectors following the U.S. government’s mandate for federal agencies to appoint Chief AI Officers.
?? The Leash Bio’s BELKA challenge aimed to develop AI models to predict the binding affinity of small molecules to protein targets using a large dataset generated by DNA-encoded chemical library technology. Despite the ambitious scope, results showed that current AI models struggle with generalization, often memorizing data rather than reasoning, which limits their effectiveness in drug discovery. This emphasizes the need for more sophisticated AI models in drug discovery—ones that can think, infer, and generalize beyond just processing large datasets.
?? On August 16, AstraZeneca’s Imfinzi (durvalumab) was approved by the FDA for treating resectable early-stage non-small cell lung cancer (NSCLC) in adults, both before and after surgery. This approval is based on the AEGEAN phase 3 trial, which showed that an Imfinzi-based regimen reduced the risk of cancer recurrence, progression, or death by 32% compared to chemotherapy alone. The trial also reported a higher rate of complete pathological response when Imfinzi was added to chemotherapy before surgery. Imfinzi is now the first immunotherapy approved for this purpose and is expected to become a key treatment option for resectable NSCLC, addressing a critical need in early-stage lung cancer treatment.
领英推荐
?? On August 16, Pfizer and BioNTech reported mixed results from their phase 3 trial of a combination mRNA vaccine targeting both influenza and COVID-19. The vaccine successfully generated strong immune responses against influenza A and COVID-19, but failed to meet the trial’s primary endpoint for neutralizing influenza B strains. This issue, common in the mRNA vaccine field, has also challenged other companies like Moderna and CureVac. Despite the setback, no safety concerns were identified, and Pfizer and BioNTech are now evaluating adjustments to enhance the vaccine’s efficacy. Additionally, Pfizer’s phase 2 trial of a next-gen trivalent mRNA flu vaccine showed robust responses against both influenza A and B, offering a potential path forward.
?? On August 16, Genentech announced it is shutting down its cancer immunology research department, leading to the departure of renowned scientist turned executive Ira Mellman after 17 years with the company. This reorganization merges the cancer immunology team with the molecular oncology group under a single oncology division, a move driven by shifts in immuno-oncology science. Mellman, who played a pivotal role in developing key therapies like Tecentriq, is leaving as a direct result of this decision. The shakeup comes after setbacks in Genentech’s anti-TIGIT program, particularly with tiragolumab failing in key lung cancer trials. While Genentech has assured that cancer immunology remains a focus, the restructuring will result in some layoffs. This change is part of broader adjustments within Genentech and its parent company, Roche, including a prior decision to cut 3% of staff.
?? On August 15, Indica Labs launched a suite of HALO AI apps, enhancing their life sciences image analysis platform with 11 new pre-trained tissue classifiers and cell phenotypers designed for various cancer types, including breast, colorectal, gastric, ovarian, and non-small cell lung cancer. These AI-powered apps, which can be customized with additional training by users, aim to streamline research by providing out-of-the-box solutions that integrate seamlessly with HALO’s existing modules. The apps offer powerful image analysis capabilities, enabling researchers to focus more on data interpretation rather than model training, thereby accelerating scientific discovery.
CLINICAL TRIAL UPDATES
?? On August 22, Sutro Biopharma announced the initiation of phase 2 REFRαME-L1 trial to evaluate its drug, luvelta, in patients with non-small cell lung cancer (NSCLC) expressing Folate Receptor-α (FRα). The trial aims to assess the safety and efficacy of luvelta in advanced or metastatic NSCLC patients. Initial results are expected in the first half of 2025.
?? On August 21, Timber Pharmaceuticals, now a subsidiary of LEO Pharma, announced disappointing results from the phase 3 ASCEND trial of TMB-001, a topical ointment for treating moderate to severe congenital ichthyosis. The trial did not meet its primary or key secondary endpoints, showing no significant difference in treatment response between TMB-001 and a placebo. Most adverse events were mild or moderate skin reactions. Due to these results, the company will not pursue a new drug application with the FDA. LEO Pharma, while committed to dermatological research, acknowledged the setback but remains focused on finding treatments for unmet medical needs.
?? On August 20, Eli Lilly announced promising results from their three-year SURMOUNT-1 phase 3 study on tirzepatide, a drug targeting adults with pre-diabetes and obesity or overweight. The study, which is the longest completed trial for tirzepatide to date, demonstrated a 94% reduction in the risk of developing type 2 diabetes in participants taking the drug compared to a placebo. Additionally, those on the highest dose of tirzepatide (15 mg) experienced a significant average weight loss of 22.9% over the treatment period. The safety profile of tirzepatide was consistent with previous studies, with the most common side effects being mild to moderate gastrointestinal issues. These results support tirzepatide’s potential as a long-term treatment for weight management and diabetes prevention.
?? On August 19, Alzamend Neuro partnered with Mass General Hospital to conduct a phase 2 clinical trial for AL001, a next-generation lithium therapeutic, aimed at treating PTSD. Led by Dr. Ovidiu Andronesi from Harvard University, the study will compare AL001 to a marketed lithium carbonate product to identify an optimal, safe, and effective dose. AL001 is designed to deliver the benefits of lithium while reducing associated toxicities, potentially eliminating the need for regular therapeutic drug monitoring. If successful, this could offer a significant improvement over current lithium treatments.
?? On August 19, the FDA granted clearance for BioNTech and Medilink to resume their phase 1 oncology trial of BNT326/YL202, a HER3-targeting antibody-drug conjugate, at a reduced dose after it was paused due to safety concerns. The trial, initially halted on June 17, 2024, due to risks of significant adverse events like decreased neutrophil count and mucositis, will now focus on a safer 3 milligram dose. This decision follows reports of promising data despite three deaths in higher dose cohorts. BioNTech’s stock rose over 6% after the announcement. The trial involves heavily pre-treated patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) or HR+/HER2-negative breast cancer. Medilink is also conducting two phase 2 trials of BNT326/YL202 in China across various cancer types. The collaboration between BioNTech and Medilink is part of a $1 billion deal, with Medilink retaining rights in China, Hong Kong, and Macau, and BioNTech holding rights elsewhere.
?? On August 16, Turn Therapeutics announced promising results from a biomarker study of their candidate GX-03, aimed at treating eczema. The study, conducted on mice, demonstrated significant inhibition of key cytokines, including IL-31, IL-36α, and IL-36γ, which are involved in the pathogenesis of dermatological conditions like atopic dermatitis. GX-03 reduced IL-31 levels by 67.7% and showed marked improvements in disease severity, as measured by the ISGA scale. The results suggest that GX-03 has strong dermal penetration and lasting effects, offering a non-steroidal, non-injectable treatment option. Turn Therapeutics plans to move forward with phase 1b/2 trials in 2025, aiming to provide a novel, safe, and effective treatment for eczema.
?? On August 16, China’s pharmaceutical regulator approved WestGene Biopharma’s new mRNA vaccine targeting Epstein-Barr virus (EBV)-positive tumors for phase 1 clinical trials. The vaccine, which had earlier received FDA approval in the U.S., has already completed early trials for cancers linked to EBV, such as nasopharyngeal carcinoma and lymphoma. WestGene Biopharma aims to further explore the vaccine’s potential in advancing tumor immunotherapy.
SCIENCE SPOTLIGHT
?? A recent study suggested that people taking semaglutide, a drug commonly used for diabetes and weight loss (marketed as Ozempic and Wegovy), may have an increased risk of experiencing suicidal thoughts compared to those on other medications. This study published by JAMA Network this Tuesday (August 20) analyzed data from a WHO database and found that patients on semaglutide had a 45% higher likelihood of reporting suicidal thoughts, with the risk being particularly elevated among those also taking antidepressants. However, the study’s findings are considered weak by some experts, who caution that the evidence does not establish a direct cause-and-effect relationship between semaglutide and suicidality.
Both the U.S. FDA and the European Medicines Agency have not found conclusive evidence linking semaglutide to increased suicide risk, though investigations are ongoing. Experts recommend cautious use of such medications, especially in individuals with a history of depression or suicidal thoughts, and suggest discontinuing the drug if new depressive symptoms emerge.
Conversely, a study from January 2024 published in Nature Medicine investigated the association between semaglutide and the risk of suicidal ideation using a large electronic health record database. The researchers conducted a retrospective cohort study involving over 240,000 patients with obesity or overweight, and replicated the analysis in nearly 1.6 million patients with type 2 diabetes.
The results showed that semaglutide was associated with a lower risk of both new and recurring suicidal thoughts compared to non-GLP1R agonist medications for obesity and diabetes. This protective effect was consistent across various demographic groups, including sex, age, and ethnicity.
?? The PALM 007 study, conducted by the NIH to evaluate SIGA’s antiviral drug tecovirimat for the treatment of mpox (monkeypox), did not achieve its primary endpoint of significantly improving lesion resolution compared to a placebo in hospitalized patients in the DRC. However, the study suggested that tecovirimat offers clinical benefits in patients treated early after symptom onset and those with severe disease. The drug maintained a strong safety profile, comparable to placebo, reinforcing its safety record established over 15 years. Despite missing the primary endpoint, SIGA and NIH are encouraged by the findings, especially the potential benefits for patients who receive treatment early or have severe cases. They plan to continue analyzing the data and conducting further trials to explore tecovirimat’s effectiveness in various patient populations and real-world settings.
ON THE HORIZON
September 2024 PDFUAs:
?? September 5: Travere Therapeutics awaiting decision on its supplemental new drug application to the FDA to convert the accelerated approval of FILSPARI (sparsentan) for treating IgA nephropathy (IgAN) into full approval.
?? September 7: Avadel Pharmaceuticals initiated a phase 3 trial of LUMRYZ for idiopathic hypersomnia and is awaiting an FDA decision by September 7, 2024, on a supplemental new drug application for pediatric narcolepsy.
?? September 18: Vanda Pharmaceuticals is awaiting FDA decision on its new drug application for tradipitant, a potential new treatment for gastroparesis.
?? September 21: In March, Zevra Therapeutics announced that the FDA has extended the review period for its new drug application for arimoclomol, a treatment for Niemann-Pick disease type C. The new PDUFA action date is 9/21.
?? September 25: Merck is expecting FDA’s decision after filing supplemental Biologics License Application for KEYTRUDA combined with chemotherapy as a first-line treatment for patients with unresectable advanced or metastatic malignant pleural mesothelioma.
?? September 26: BMS is anticipating a crucial FDA decision by September 26, 2024, on KarXT (xanomeline-trospium), a novel antipsychotic treatment for schizophrenia. Acquired through BMS’s March 2024 purchase of Karuna Therapeutics, KarXT represents the first new drug class for schizophrenia in several decades.
?? September 27: The FDA has granted Priority Review to Sanofi’s Sarclisa (isatuximab) for use in combination with standard-of-care treatment (bortezomib, lenalidomide, and dexamethasone, or VRd) for newly diagnosed multiple myeloma patients who are ineligible for transplant.
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DISCLAIMER: This content is for informational purposes only. It should not be taken as legal, tax, investment, financial, or other advice. The views expressed here are my own and do not reflect the opinions of any company or institution.
DISCLOSURE: I have no business relationships with any company mentioned in this article.