On November 11, 2024 23andMe Holding Co. (Nasdaq: ME) (the "Company" or "23andMe"), a leading human genetics and preventive health company, reported a business restructuring to streamline operations and reduce costs (Press release, 23andMe, NOV 11, 2024, View Source [SID1234651087]). In addition, 23andMe is discontinuing further development of all its therapeutics programs, while evaluating strategic alternatives for its clinical and preclinical assets.

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The Company is reducing its overall headcount by over 200 employees, representing approximately 40% of the workforce. The business restructuring is expected to substantially reduce operating expenses and result in annualized cost savings of more than $35 million. The Company expects to incur up to $12 million in costs and expenses primarily related to one-time severance, transition and termination-related costs.

"We are taking these difficult but necessary actions as we restructure 23andMe and focus on the long-term success of our core consumer business and research partnerships," said Anne Wojcicki, 23andMe’s CEO, Co-Founder, and Chair of the Board. "I want to thank our team for their hard work and dedication to our mission. We are fully committed to supporting the employees impacted by this transition."

Strategic Alternatives Process for Therapeutics Programs

In parallel with the discontinuation of its therapeutics division, the Company is actively exploring all strategic options for a limited time to maximize the value of its therapeutics programs, including licensing agreements, asset sales or other transactions. 23andMe intends to wind-down its ongoing clinical trials as quickly as practical, while the strategic alternatives process is ongoing.

"We continue to believe in the promise shown by our clinical and preclinical stage pipeline and will continue to pursue strategic opportunities to continue their development. We remain deeply grateful to the patients, investigators and study staff for their participation in our clinical trials," said Wojcicki.

The Company’s therapeutic programs include 23ME-00610 (a Phase 1/2a therapeutic antibody that is designed to restore the immune system’s ability to kill cancer cells by blocking the immune checkpoint CD200R1), 23ME-01473 (a Phase 1 therapeutic antibody that targets ULBP6, which can be expressed and secreted by tumor cells to suppress immune activity), and other preclinical immunology and inflammation programs. 23ME-00610 has demonstrated early monotherapy responses, potential patient selection biomarkers, and combination potential for patients across multiple difficult-to-treat solid tumors and 23ME-01473 has yielded promising preclinical data with a novel NK-cell-activating mechanism.

There can be no assurance that the strategic alternatives process for the therapeutics assets will result in any course of action and there is no definitive timeline for completion.

About 23ME-00610 (Phase 1/2a)
23ME-00610 is a monoclonal antibody that binds to CD200R1 to prevent the interaction of CD200R1 with CD200. Using the world’s largest proprietary database of health and genetic information, 23andMe identified genetic variants of CD200R1, CD200, and DOK2, the downstream signaling protein, associated with higher risks of immune disease and lower risks of cancer, pinpointing CD200R1 as a promising immuno-oncology target.

23ME-00610 has demonstrated preliminary evidence of clinical benefit as monotherapy, including partial responses by RECIST criteria in patients with neuroendocrine tumors and clear-cell renal-cell carcinomas in the Phase 1/2a clinical trial. Additional preclinical data and recent literature validate the CD200-CD200R1 pathway as a potential oncology target for reversing immune tolerance, as a monotherapy or in combination (e.g., with anti-PD-1, anti-VEGF, CAR-T cell therapies). Higher tumor expression of CD200 and human genetics correlated with increased clinical benefit, suggesting potential value as patient selection biomarkers.

23ME-00610 has shown favorable pharmacokinetics (PK) for dosing once every three weeks, expected on-target pharmacologic activity, and a promising safety and tolerability profile suggesting amenability to combination therapies.

About 23ME-01473 (Phase 1)
23ME-01473 targets ULBP6 to restore anti-tumor immunity through NK and T cells. ULBPs are stress-induced ligands found on the surface of cancer cells that bind to their receptor, NKG2D, on NK and T cells. Cancers escape immune cell recognition by shedding decoy ULBP ligands from their cell surface. ULBP6 has the highest binding affinity to NKG2D, potentially 30 times higher than MICA.

Blocking the binding of soluble ULBP6 to NKG2D through ‘1473 may restore immune cell recognition and killing of cancer cells. ‘1473 is also Fc-effector enhanced, which further enables NK cells to induce cell death of ULBP6-expressing cancer cells.

ULBP6 was identified as a potential cancer drug target using the 23andMe immuno-oncology (I/O) genetic signature, an approach developed by 23andMe to identify evidence for genetic variants that increase immune function while decreasing cancer risk. Using genetic data, 23andMe can identify immune-related genes that are expected to have an impact on cancer biology. Specifically, germline genetics can reveal which of the immune-related genes harbor genetic variants that also alter an individual’s predisposition for developing cancer.

On November 11, 2024 Assertio Holdings, Inc. ("Assertio" or the "Company") (Nasdaq: ASRT), a pharmaceutical company with comprehensive commercial capabilities offering differentiated products to patients, reported financial results for the third quarter ended September 30, 2024 (Press release, Assertio Holdings, NOV 11, 2024, View Source [SID1234649320]).

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"Third quarter results reflected solid performance as we continue to establish Rolvedon as our lead asset and drive economic returns from our commercial portfolio," said Brendan O’Grady, Chief Executive Officer. "Rolvedon has been well received by physicians, posting another quarter of stable performance and the continued expansion of our customer base. The Rolvedon same day dosing trial has concluded and the results have been accepted for presentation at the San Antonio Breast Cancer Symposium in December 2024."

"Additionally, we have implemented new sales and marketing tactics for Sympazan, which are designed to drive prescriber awareness and prescription growth in key markets. We are maintaining our share of Indocin and working to maximize the value of this product and our other commercial assets moving forward. We are also evaluating new approaches to grow existing assets as well as the acquisition of additional assets to fuel further growth."

On November 11, 2024 NuCana plc (NASDAQ: NCNA) reported that initial data from the ongoing Phase 1b/2 modular study (NuTide:303) investigating NUC-3373 in combination with the PD-1 inhibitor pembrolizumab for patients with advanced solid tumors (Module 1) and in combination with docetaxel for patients with lung cancer (Module 2) have been published in MedRxiv, the preprint server for Health Sciences (Press release, Nucana, NOV 11, 2024, View Source [SID1234648580]).

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Module 1 included 12 patients with a variety of solid tumors who had exhausted all other treatment options. The majority of patients (n=9) had received prior PD-(L)1 based therapy. Encouraging signals of anti-cancer activity were observed with confirmed Partial Responses in 2 patients and Stable Disease in a further four patients, resulting in an objective response rate of 22% and a disease control rate of 67% in the efficacy evaluable population. The combination of NUC-3373 plus pembrolizumab was generally well tolerated.

Module 1 Selected Case Studies: NUC-3373 plus pembrolizumab in patients with advanced solid tumors

72-year-old patient with urothelial bladder cancer (Lynch syndrome) who had previously received gemcitabine plus cisplatin followed by the PD-L1 inhibitor atezolizumab (achieved a Partial Response and remained on therapy for 23 months). Following treatment with NUC-3373 plus pembrolizumab, the patient achieved 100% reduction in the target lesion (considered a confirmed Partial Response due to the presence of non-target lesions) and remains on treatment for over 10 months.
75-year-old patient with BRAF mutant metastatic cutaneous melanoma who had previously received pembrolizumab (best response of Progressive Disease within 5 months) followed by dabrafenib plus trametinib (discontinued trametinib after 1 month due to toxicity and achieved Stable Disease before progressing after seven years on dabrafenib). Following treatment with NUC-3373 plus pembrolizumab, this patient achieved a confirmed Partial Response with an 81% reduction in the target lesion and remains on treatment for over 12 months.
Module 2 included 4 patients with non-small cell lung cancer (NSCLC) or pleural mesothelioma who had disease progression on, or were unable to tolerate, prior chemotherapy-containing regimens. Docetaxel is the current standard of care for NSCLC patients without targetable alterations who progress on PD-(L)1 inhibitor-based therapy, however, it is associated with modest clinical benefit (median PFS of 3-4 months) and substantial toxicity. Following treatment of the first 4 patients in this module, enrollment was put on hold due to toxicity challenges with docetaxel. Despite this, 2 patients achieved prolonged Stable Disease. Protocol modifications to include the use of a different taxane in this combination are currently being considered.

Module 2 Selected Case Studies: NUC-3373 plus docetaxel in patients with lung cancer

60-year-old patient with pleural mesothelioma who had previously received carboplatin plus pemetrexed (progressed within 4 months), the PD-1 inhibitor nivolumab (progressed within 4 months), and carboplatin plus pemetrexed (progressed within 1 month). Following treatment with NUC-3373 plus docetaxel, the patient achieved Stable Disease for more than 13 months (ongoing).
77-year-old patient with squamous NSCLC who had previously received carboplatin plus paclitaxel plus pembrolizumab (Stable Disease for 2 months) followed by maintenance pembrolizumab (progressed within 21 months). Following treatment with NUC-3373 plus docetaxel, the patient achieved Stable Disease for 7 months.
Full details can be found in the publication: Link

Professor David Harrison, NuCana’s Head of Translational Medicine, stated: "We previously presented data on NUC-3373’s ability to elicit the release of Damage Associated Molecular Patterns (DAMPs), promote an anti-tumor immune response, and potentiate the activity of PD-1 inhibitors in human cancer cell lines. These data led us to investigate the combination of NUC-3373 plus pembrolizumab so we are very excited to observe these encouraging clinical findings in PD-(L)1 inhibitor experienced patients."

Professor Harrison continued: "We have also demonstrated that NUC-3373 is a very potent thymidylate synthase inhibitor and causes DNA damage, leading us to hypothesize that NUC-3373 may be an attractive alternative to pemetrexed in patients with NSCLC and mesothelioma. Observing that NUC-3373 in combination with docetaxel is stabilizing disease in these hard-to-treat patient populations provides further evidence supporting this hypothesis."

Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer, said: "We are very excited that these NUC-3373 combinations have been observed to provide a meaningful clinical benefit to patients who had exhausted all other treatment options. We recently presented encouraging efficacy and safety data at ESMO (Free ESMO Whitepaper) on NUC-7738 plus pembrolizumab in patients with metastatic melanoma who were refractory or resistant to PD-1 inhibitors. We are pleased to have two Phase 2 product candidates in our portfolio, each with a distinct mechanism of action, that can potentiate PD-1 inhibitors in PD-(L)1 resistant patients. We look forward to sharing additional data from the NuTide:303 study and our clinical development plans for both NUC-3373 and NUC-7738 in the near future."

On November 11, 2024, Allogene Therapeutics, Inc. (the "Company") reported the company decided to discontinue enrollment in its Phase 1 cohort in the ALPHA2 clinical trial to evaluate cemacabtagene ansegedleucel ("cema-cel") as a treatment for relapsed or refractory chronic lymphocytic leukemia (CLL) in patients previously treated with BTKi and BCL2i therapies (Press release, Allogene, NOV 11, 2024, View Source [SID1234648244]). While there is an ongoing need for additional treatment options for these patients, and interest in this cohort remains high among investigators, enrollment in the trial has been slower than anticipated due in part to the emergence of new alternative treatment options. Consequently, the Company is discontinuing enrollment in this trial and reallocating resources to other programs.

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On November 11, 2024 NuCana plc (NASDAQ: NCNA) reported that initial data from the ongoing Phase 1b/2 modular study (NuTide:303) investigating NUC-3373 in combination with the PD-1 inhibitor pembrolizumab for patients with advanced solid tumors (Module 1) and in combination with docetaxel for patients with lung cancer (Module 2) have been published in MedRxiv, the preprint server for Health Sciences (Press release, Nucana, NOV 11, 2024, View Source [SID1234648195]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Module 1 included 12 patients with a variety of solid tumors who had exhausted all other treatment options. The majority of patients (n=9) had received prior PD-(L)1 based therapy. Encouraging signals of anti-cancer activity were observed with confirmed Partial Responses in 2 patients and Stable Disease in a further four patients, resulting in an objective response rate of 22% and a disease control rate of 67% in the efficacy evaluable population. The combination of NUC-3373 plus pembrolizumab was generally well tolerated.

Module 1 Selected Case Studies: NUC-3373 plus pembrolizumab in patients with advanced solid tumors

•
72-year-old patient with urothelial bladder cancer (Lynch syndrome) who had previously received gemcitabine plus cisplatin followed by the PD-L1 inhibitor atezolizumab (achieved a Partial Response and remained on therapy for 23 months). Following treatment with NUC-3373 plus pembrolizumab, the patient achieved 100% reduction in the target lesion (considered a confirmed Partial Response due to the presence of non-target lesions) and remains on treatment for over 10 months.

•
75-year-old patient with BRAF mutant metastatic cutaneous melanoma who had previously received pembrolizumab (best response of Progressive Disease within 5 months) followed by dabrafenib plus trametinib (discontinued trametinib after 1 month due to toxicity and achieved Stable Disease before progressing after seven years on dabrafenib). Following treatment with NUC-3373 plus pembrolizumab, this patient achieved a confirmed Partial Response with an 81% reduction in the target lesion and remains on treatment for over 12 months.

Module 2 included 4 patients with non-small cell lung cancer (NSCLC) or pleural mesothelioma who had disease progression on, or were unable to tolerate, prior chemotherapy-containing regimens. Docetaxel is the current standard of care for NSCLC patients without targetable alterations who progress on PD-(L)1 inhibitor-based therapy, however, it is associated with modest clinical benefit (median PFS of 3-4 months) and substantial toxicity. Following treatment of the first 4 patients in this module, enrollment was put on hold due to toxicity challenges with docetaxel. Despite this, 2 patients achieved prolonged Stable Disease. Protocol modifications to include the use of a different taxane in this combination are currently being considered.

Module 2 Selected Case Studies: NUC-3373 plus docetaxel in patients with lung cancer

•
60-year-old patient with pleural mesothelioma who had previously received carboplatin plus pemetrexed (progressed within 4 months), the PD-1 inhibitor nivolumab (progressed within 4 months), and carboplatin plus pemetrexed (progressed within 1 month). Following treatment with NUC-3373 plus docetaxel, the patient achieved Stable Disease for more than 13 months (ongoing).

•
77-year-old patient with squamous NSCLC who had previously received carboplatin plus paclitaxel plus pembrolizumab (Stable Disease for 2 months) followed by maintenance pembrolizumab (progressed within 21 months). Following treatment with NUC-3373 plus docetaxel, the patient achieved Stable Disease for 7 months.

Full details can be found in the publication: Link

Professor David Harrison, NuCana’s Head of Translational Medicine stated: "We previously presented data on NUC-3373’s ability to elicit the release of Damage Associated Molecular Patterns (DAMPs), promote an anti-tumor immune response, and potentiate the activity of PD-1 inhibitors in human cancer cell lines. These data led us to investigate the combination of NUC-3373 plus pembrolizumab so we are very excited to observe these encouraging clinical findings in PD-(L)1 inhibitor experienced patients."

Professor Harrison continued: "We have also demonstrated that NUC-3373 is a very potent thymidylate synthase inhibitor and causes DNA damage, leading us to hypothesize that NUC-3373 may be an attractive alternative to pemetrexed in patients with NSCLC and mesothelioma. Observing that NUC-3373 in combination with docetaxel is stabilizing disease in these hard-to-treat patient populations provides further evidence supporting this hypothesis."

Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer said: "We are very excited that these NUC-3373 combinations have been observed to provide a meaningful clinical benefit to patients who had exhausted all other treatment options. We recently presented encouraging efficacy and safety data at ESMO (Free ESMO Whitepaper) on NUC-7738 plus pembrolizumab in patients with metastatic melanoma who were refractory or resistant to PD-1 inhibitors. We are pleased to have two Phase 2 product candidates in our portfolio, each with a distinct mechanism of action, that can potentiate PD-1 inhibitors in PD-(L)1 resistant patients. We look forward to sharing additional data from the NuTide:303 study and our clinical development plans for both NUC-3373 and NUC-7738 in the near future."