Itacitinib

Oncternal Therapeutics is laying off about ten employees, representing approximately 37% of its workforce. Credit: Andrii Yalanskyi via Shutterstock. Oncternal Therapeutics ’s stock has slumped after the company announced it is dropping its clinical trials and will lay off staff to save cash. The US-based biotech is discontinuing its clinical trials evaluating ONCT-534, a dual action androgen receptor inhibitor for metastatic castration-resistant prostate cancer, and ONCT-808, a ROR1-targeting autologous CAR-T candidate for patients with aggressive B-cell lymphoma. The biotech’s stock plummeted by 60%, dropping from $4.17 per share before market close on 11 September to $1.70 at market close on 12 September, the day of the announcement. This update comes after ONCT-534 failed to perform in the interim Phase I trial (NCT05917470) results. In the 20 enrolled patients, ONCT-534 did not show clinically meaningful improvements in disease, including prostate-specific antigen (PSA) levels. The patients were treated in eight dosing cohorts with varying schedules of administration and doses. In December 2023, Oncternal reported the death of a patient in a Phase I/II dose escalation study (NCT05588440) of B-cell lymphoma therapy ONCT-808. The patient, who was the first to receive a higher dose level in the study, died after showing signs consistent with cytokine release syndrome, as well as immune effector cell-associated neurotoxicity syndrome, said Oncternal. See Also: Itacitinib adipate by Incyte for Acute Myelocytic Leukemia (AML, Acute Myeloblastic Leukemia): Likelihood of Approval Itacitinib adipate by Incyte for Non-Hodgkin Lymphoma: Likelihood of Approval Oncternal’s CEO James Breitmeyer said: “The early results during dose escalation in the Phase I/II studies of ONCT-534 in heavily pretreated patients are disappointing, as the study was supported by extensive preclinical data and was designed to address important unmet medical needs for patients with advanced prostate cancer.” While Oncternal plans to explore alternative options for the programmes, it will discontinue all product development activities and take other steps to reduce costs, including reducing its workforce. In a 12 September SEC filing, Oncternal shared that it will slash its workforce by 37%. The layoffs – which it expects to complete by Q3 2024 – are estimated to incur workforce reduction-related charges of about $1m. The latest news adds to a string of failures from the company that terminated two trials investigating its tyrosine kinase inhibitor (TKI) zilovertamab in April 2023 to free up cash. One of these was a Phase III study that investigated the TKI in combination with Johnson & Johnson and AbbVie ’s blockbuster TKI Imbruvica (ibrutinib) in mantle cell lymphoma.

Moderna announced highlights, progress, and strategic priorities in its annual R&D day event. Credit: Tada Images via Shutterstock. Moderna will cut five clinical programmes amid plans to reduce $1.1bn of R&D costs following years of declining revenues. The company highlighted its rejig in priorities at its annual R&D day, saying that it will expand its commercial portfolio into oncology, rare diseases, and first-in-class non-respiratory vaccines, a strategy it hopes will generate ten product approvals over the next three years. The product launches include vaccines for Covid-19, flu, cytomegalovirus, norovirus, melanoma, and others. Investor response was tepid, however, with the mRNA specialist’s stock opening 19% lower than yesterday (11 September).  It has since recovered slightly. This announcement is the latest in a series of measures by Moderna to find its feet after its dwindling success from the Covid-19 pandemic. The company reported a net loss of $4.7bn for FY 2023, blaming a decline in sales of its Covid-19 vaccine, Spikevax. The company is advancing programmes in non-respiratory conditions in addition to its Covid-19 and flu vaccines, despite stating plans to move away from Covid-19. While the company is advancing these programmes, it has slashed five others. It has discontinued preclinical mRNA-1287, a vaccine candidate against the four endemic human coronaviruses. Four Phase I candidates will also be dropped: mRNA-0184 for congestive heart failure, mRNA-5671, a KRAS-targeting cancer vaccine, cancer drug mRNA-2752, and its respiratory syncytial virus (RSV) vaccine mRESVIA (mRNA-1345) in infants. See Also: Itacitinib adipate by Incyte for Acute Myelocytic Leukemia (AML, Acute Myeloblastic Leukemia): Likelihood of Approval Itacitinib adipate by Incyte for Non-Hodgkin Lymphoma: Likelihood of Approval In June, Moderna’s RSV vaccine mRESVIA secured US Food and Drug Administration (FDA) approval for adults over the age of 60. This marked the first approval of an mRNA vaccine for a disease other than Covid-19, and Moderna’s second product to be approved. In the 12 September update, the company announced positive Phase III results for mRESVIA in 18–59-year-olds, sharing that the vaccine met all primary immunogenicity endpoints. Moderna said it now plans to submit a supplemental biologic licence application (sBLA) for US approval later this year. Moderna also said it plans to break even on an operating cash cost basis in 2028, two years later than the previously announced goal of 2026. In the announcement accompanying the progress and strategic priorities, Moderna’s CEO Stéphane Bancel said: “Moderna now has five respiratory vaccines with positive Phase III results and expects to submit three for approval this year. In addition, we have five non-respiratory products in pivotal studies across cancer, rare diseases, and latent vaccines with potential for approval by 2027. “The size of our late-stage pipeline combined with the challenge of launching products means we must now focus on delivering these ten products to patients, slow down the pace of new R&D investment, and build our commercial business.”