On November 12, 2024 Bolt Biotherapeutics (Nasdaq: BOLT), a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer, reported financial results for the third quarter ended September 30, 2024, and provided a business update (Press release, Bolt Biotherapeutics, NOV 12, 2024, View Source [SID1234648159]).

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"During the third quarter, we continued to make progress with our two proprietary programs, BDC-3042 and BDC-4182," said Willie Quinn, Chief Executive Officer. "We have now completed the sixth dose level in the first-in-human clinical trial of BDC-3042, have opened the final cohort which will study a dose level of 10 mg/kg, and expect to provide a data update in the first half of 2025. We are particularly excited about our next-generation ISAC BDC-4182, which builds on the lessons we learned from our clinical experience with BDC-1001. We believe that BDC-4182’s dramatic increase in potency and activity will potentially enable the treatment of patients whose tumors have lower claudin 18.2 expression and may provide even better anti-tumor activity than conventional ADCs. We presented some of the data that underlies this excitement at SITC (Free SITC Whitepaper), and the team is hard at work preparing for a clinical trial initiation of BDC-4182 in the second quarter next year."

Recent Highlights and Anticipated Milestones

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Presented updated clinical activity of BDC-4182 at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). BDC-4182 is a next-generation BoltbodyTMISAC clinical candidate targeting claudin 18.2, a novel, clinically validated target in oncology with expression in gastric/gastroesophageal junction cancer, pancreatic cancer, and other tumor types. BDC-4182 has advanced into IND-enabling activities, supported by in vitro and in vivo experiments demonstrating potent anti-tumor activity in multiple preclinical models, with clinical trial initiation expected in 2025. BDC-4182 was well tolerated in non-human primates at the highest dose tested (12mg/kg) with an acceptable safety profile. BDC-4182 outperformed cytotoxic claudin 18.2 ADCs in syngeneic models and BDC-4182’s favorable toxicology profile enables a variety of potential future combinations.

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Presented key learnings from Phase 1 dose-escalation trial of BDC-1001 at SITC (Free SITC Whitepaper). First-generation ISAC BDC-1001 demonstrated immunological activity in this first-in-human trial, particularly in patients with high HER2 antigen expression. Greater immune activation appeared to be associated with clinical benefit. Pharmacodynamic changes were observed in patients whose tumors had higher levels of HER2 and were statistically significant in patients with HER2 IHC 3+ tumors. Data supports the hypothesis that an ISAC with enhanced immune activation could offer greater efficacy, warranting further testing in next-generation ISACs.
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Advanced to cohort 7 (10 mg/kg) in the Phase 1 study of BDC-3042 in patients with advanced cancers. BDC-3042 is a proprietary agonist antibody that targets Dectin-2, an immune-activating receptor expressed by tumor-associated macrophages (TAMs). This single-agent, dose-escalation Phase 1 clinical study is evaluating BDC-3042 in patients with metastatic or unresectable triple-negative breast cancer (TNBC), colorectal cancer, clear cell renal cell carcinoma, head and neck cancer, non-small cell lung cancer (NSCLC), ovarian cancer, or melanoma.
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Collaborations with Genmab and Toray continue to progress. The Company continues to work with its collaborators to discover and develop ISACs for the treatment of cancer.
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Cash, cash equivalents, and marketable securities were $84.4 million as of September 30, 2024. Cash on hand is expected to fund multiple milestones and operations through mid-2026.

Third Quarter 2024 Financial Results

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Collaboration Revenue – Collaboration revenue was $1.1 million for the quarter ended September 30, 2024, compared to $2.5 million for the same quarter in 2023. Revenue in the comparative periods was generated from services performed under the R&D collaborations as we fulfill our performance obligations.

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Research and Development (R&D) Expenses – R&D expenses were $13.8 million for the quarter ended September 30, 2024, compared to $15.0 million for the same quarter in 2023. The decrease between the comparable periods was mainly due to a decrease in salary and related expenses primarily as a result of the May 2024 restructuring partially offset by an increase in contract manufacturing expenses.

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General and Administrative (G&A) Expenses – G&A expenses were $3.8 million for the quarter ended September 30, 2024, compared to $5.8 million for the same quarter in 2023. The decrease between the comparable periods was mainly due to a decrease in salary and related expenses primarily as a result of the May 2024 restructuring.

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Loss from Operations – Loss from operations was $16.4 million for the quarter ended September 30, 2024, compared to $18.2 million for the same quarter in 2023.

About the Boltbody Immune-Stimulating Antibody Conjugate (ISAC) Platform
Bolt Biotherapeutics’ Boltbody ISAC platform harnesses the precision of antibodies with the power of the innate and adaptive immune system to generate a productive anti-cancer response. Each Boltbody ISAC candidate comprises a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant. The antibody is designed to target one or more markers on the surface of a tumor cell and the immune stimulant is designed to recruit and activate myeloid cells. Activated myeloid cells initiate a positive feedback loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This increases the population of activated immune system cells in the tumor microenvironment and promotes a robust immune response with the goal of generating durable therapeutic responses for patients with cancer.

On November 12, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, reported financial results and corporate updates from the third quarter of 2024 (Press release, BeiGene, NOV 12, 2024, View Source [SID1234648158]).

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"Our exceptional third-quarter results underscore the Company’s global oncology leadership driven by our unique R&D and clinical advantages as well as the tremendous launch trajectory of BRUKINSA," said John V. Oyler, Co-Founder, Chairman and CEO at BeiGene. "In the U.S., BRUKINSA, with the broadest label of any BTK inhibitor, is now the leader in new patient starts in both frontline and relapsed/refractory (R/R) CLL in addition to all other approved B-cell malignancies. As the cornerstone of our hematology franchise, BRUKINSA shows tremendous promise for patients as a monotherapy and as a backbone for best-in-class combinations with our late-stage BCL2 inhibitor, sonrotoclax, and BTK degrader BGB-16673. In the solid tumor area, we’re expanding access to our PD-1 inhibitor, TEVIMBRA, for patients worldwide and building global commercial capabilities to support our prolific pipeline of exciting potential cancer medicines. We are laying the foundation for future franchises in breast, lung, and gastrointestinal cancers across three signature platform technologies including multi-specific antibodies, protein degraders, and antibody-drug conjugates. This progress not only highlights our achievements but also emphasizes our commitment to positively impacting patients’ lives globally, fostering hope and advancements in the fight against cancer."

On November 12, 2024 Aura Biosciences, Inc. (NASDAQ: AURA), a clinical-stage biotechnology company developing precision therapies for solid tumors designed to preserve organ function, reported financial results for the third quarter ended September 30, 2024, and provided recent business highlights (Filing, 3 mnth, SEP 30, Aura Biosciences, 2024, NOV 12, 2024, View Source [SID1234648157]).

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"This is a transformative time for our Company, as we presented the first positive data in NMIBC, which we believe provides clinical evidence of the potential of bel-sar in solid tumors beyond the eye," said Elisabet de los Pinos, PhD, Chief Executive Officer of Aura Biosciences. "We believe that bel-sar’s innovative mechanism of action may provide the first immune-ablative treatment in bladder cancer, with the goal to potentially offer safe and durable responses with a focal approach that is easily delivered by urologists in the office."

In addition to positive early data from an ongoing Phase 1 trial of bel-sar in patients with NMIBC, the Company also recently presented positive Phase 2 end of study data in early-stage choroidal melanoma and continues to progress the ongoing Phase 3 CoMpass trial.

"I am excited for bel-sar’s potential for patients who are diagnosed with indeterminate lesions or small choroidal melanoma where we currently have no good treatment options. We either wait for the disease to progress or treat with radiation, which leads to irreversible vision loss," said Carol L. Shields, MD, Chief of the Ocular Oncology Service at Wills Eye Hospital and Professor of Ophthalmology at Thomas Jefferson University in Philadelphia. "If approved, bel-sar may represent the opportunity to treat choroidal melanoma at an earlier stage of medical intervention and set a new standard of care in a disease that has had no new therapies approved for decades."

On November 12, 2024 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, reported financial results for the third quarter 2024, recent business highlights, and key upcoming milestones (Press release, Atara Biotherapeutics, NOV 12, 2024, View Source [SID1234648156]).

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"With the first patient now enrolled in our Phase 1 NHL trial of ATA3219, we have taken an important step in applying our proven Epstein-Barr virus platform to the significant opportunity in allogeneic CAR T," said Cokey Nguyen, Ph.D., President and Chief Executive Officer of Atara. "The first quarter of 2025 is positioned to be transformational for the company, with the potential for FDA approval of tab-cel and transition of this business to our partner Pierre Fabre, repositioning Atara as a fully focused allogeneic CAR-T company with multiple near-term data milestones for our lead program in oncology and autoimmune indications."

Tabelecleucel (tab-cel or EbvalloTM) for Post-Transplant Lymphoproliferative Disease (PTLD)

Tab-cel biologics license application (BLA) is on track with Priority Review and a Prescription Drug User Fee Act (PDUFA) target action date of January 15, 2025
A U.S. Food and Drug Administration (FDA) advisory committee meeting is not planned
Atara has the potential to receive an additional $60 million milestone payment from Pierre Fabre contingent upon FDA approval of the tab-cel BLA
ATA3219: CD19 Program in Non-Hodgkin’s Lymphoma (NHL)

First patient treated in ongoing Phase 1 clinical study of ATA3219 for NHL, including large B-cell lymphomas, follicular lymphoma, and mantle cell lymphoma
Study designed to evaluate safety, preliminary efficacy, pharmacokinetics, and biomarkers
Initial clinical data anticipated in Q1 2025
ATA3219: CD19 Program in Lupus Nephritis (LN)

Atara expects to initiate a Phase 1 study of ATA3219 as a monotherapy for the treatment of systemic lupus erythematosus (SLE) with kidney involvement (lupus nephritis [LN]) by end of year with initial clinical data anticipated in mid-2025
ATA3219: CD19 Program in Extrarenal Systemic Lupus Erythematosus (ERL) Without Lymphodepletion (LD)

Atara expanded the Phase 1 LN study of ATA3219 with an additional cohort in ERL without LD, and expects initiation by end of year with initial clinical data anticipated in mid-2025
The elimination of LD is designed to further simplify the treatment regimen and to potentially provide a differentiated safety profile to patients without comprising efficacy, which may improve patient access
ATA3431: CD19/CD20 Program for B-Cell Malignancies

Atara is progressing toward an IND submission in Q4 2025
Leadership and Board of Directors Update

As previously announced, on September 9, 2024, Cokey Nguyen, Ph.D. became President and CEO and Pascal Touchon assumed the role of Chairman of the Board of Directors
Greg Ciongoli, founder and managing partner of Adiumentum Capital Management, joined Atara’s Board of Directors
Eric Hyllengren has been appointed to serve as the Company’s Chief Operating Officer, in addition to his role as Chief Financial Officer
Third Quarter 2024 Financial Results

Cash, cash equivalents and short-term investments as of September 30, 2024 totaled $67.2 million, as compared to $35.3 million as of June 30, 2024. This includes a $20 million milestone payment related to the tab-cel BLA acceptance that was received from Pierre Fabre in August 2024, $15.5 million from Pierre Fabre for the purchase of certain existing tab-cel intermediate inventory in September 2024, and gross proceeds of $36 million from a registered direct offering completed in September 2024. The financing was led by existing top institutional investors with participation from a new strategic investor and was completed at a 15% premium to Atara’s 7-day volume-weighted average price
Net cash used in operating activities was $4.0 million for the third quarter 2024, as compared to $51.3 million in the same period in 2023
Q3 2024 net cash used in operating activities included a $6.0 million sub-licensing fee payment, which was paid to Memorial Sloan Kettering Cancer Center (MSK) under protest, as Atara does not believe it owes this under the terms of its license agreements with MSK. Atara is entering into evaluative non-binding mediation to potentially resolve this disagreement
Total revenues were $40.2 million for the third quarter 2024, as compared to $2.1 million for the same period in 2023. Total revenues increased by $38.1 million year over year, primarily due to revenue recognized as a result of additional obligations for the expanded partnership with Pierre Fabre and accelerated recognition of existing deferred revenue due to the planned transition of substantially all activities relating to tab-cel at the time of BLA approval and transfer to Pierre Fabre
Total costs and operating expenses include non-cash stock-based compensation, depreciation and amortization expenses of $7.7 million for the third quarter 2024, as compared to $12.4 million for the same period in 2023
Research and development expenses were $43.9 million for the third quarter 2024, as compared to $56.9 million for the same period in 2023
Research and development expenses include a $6.0 million sub-licensing fee, which was paid to MSK under protest, whereas third quarter 2023 had no such comparable expense
Research and development expenses also include $2.9 million of non-cash stock-based compensation expenses for the third quarter 2024, as compared to $6.8 million for the same period in 2023
General and administrative expenses were $10.4 million for the third quarter 2024, as compared to $12.2 million for the same period in 2023
General and administrative expenses include $3.5 million of non-cash stock-based compensation expenses for the third quarter 2024, as compared to $4.4 million for the same period in 2023
Atara reported net losses of $21.9 million, or $2.93 per share, for the third quarter 2024, as compared to $69.8 million, or $16.40 per share, for the same period in 2023
2024 Outlook and Cash Runway

Atara expects full year 2024 operating expenses to decrease by approximately 35% from 2023
The large majority of the year-over-year operating expense reduction began in Q2 2024 and is expected to continue for the remainder of the year
Atara expects that cash, cash equivalents, short-term investments, and accounts receivable as of September 30, 2024, plus the items noted below, in total will enable funding of planned operations into 2027:
additional $60 million approval milestone from Pierre Fabre contingent upon the approval of the tab-cel BLA;
additional anticipated purchases of tab-cel inventory through the manufacturing transfer date by Pierre Fabre;
anticipated reimbursement for tab-cel global development costs through the BLA transfer by Pierre Fabre;
operating efficiencies resulting from completed workforce reductions;
the planned transition of substantially all activities relating to tab-cel at the time of the BLA transfer to Pierre Fabre potentially as early as Q1 2025, which will further reduce quarterly operating expenses; and
anticipated royalties from sales of tab-cel by Pierre Fabre in the U.S. post BLA approval
About ATA3219

ATA3219 combines the natural biology of unedited T cells with the benefits of an allogeneic therapy. It consists of allogeneic Epstein-Barr virus (EBV)-sensitized T cells that express a CD19 CAR construct for the treatment of CD19+ relapsed or refractory B-cell malignancies, including B-cell non-Hodgkin’s lymphoma and B-cell mediated autoimmune diseases including systemic lupus erythematosus. ATA3219 has been optimized to offer a potential best-in-class profile, featuring off-the-shelf availability. It incorporates multiple clinically validated technologies including a modified CD3ζ signaling domain (1XX) that optimizes expansion and mitigates exhaustion, enrichment during manufacturing for a less differentiated phenotype for robust expansion and persistence and retains the endogenous T-cell receptor without gene editing as a key survival signal for T cells contributing to persistence.

About ATA3431

ATA3431 is an allogeneic, bispecific CAR directed against CD20 and CD19, built on Atara’s EBV T-cell platform. The design consists of a tandem CD20-CD19 design, with binders oriented to optimize potency. Dual targets address the limitations of single antigen loss and tumor variability. ATA3431 features a novel 1XX signaling domain, memory phenotype, and retained, unedited T-cell receptor. Preclinical data have demonstrated early evidence of antitumor activity, long-term persistence, and superior tumor growth inhibition compared to an autologous CD19/CD20 CAR T benchmark.

Next-Generation Allogeneic CAR T Approach

Atara is focused on applying Epstein-Barr virus (EBV) T-cell biology, featuring experience in over 600 patients treated with allogeneic EBV T cells, and novel chimeric antigen receptor (CAR) technologies to meet the current limitations of autologous and allogeneic CAR therapies head-on by advancing a potential best-in-class CAR T pipeline in oncology and autoimmune disease. Unlike gene-edited approaches aimed at inactivating T-cell receptor (TCR) function to reduce the risk for graft-vs-host disease, Atara’s allogeneic platform maintains expression of the native EBV TCR that promotes in vivo functional persistence while also demonstrating inherently low alloreactivity due to their recognition of defined viral antigens and partial human leukocyte antigen (HLA) matching. A molecular toolkit of clinically-validated technologies—including the 1XX signaling domain designed for better cell fitness and less exhaustion while maintaining stemness—offers a differentiated approach to addressing significant unmet need with the next generation CAR T.

On November 12, 2024 Alentis Therapeutics ("Alentis"), the clinical-stage biotechnology company developing treatments for Claudin-1 positive (CLDN1+) tumors and organ fibrosis, reported that it has raised $181.4 million in Series D financing, supported by a syndicate of top-tier biotech investors (Press release, Alentis Therapeutics, NOV 12, 2024, View Source [SID1234648155]). The financing will support Alentis to develop a deep pipeline of CLDN1 targeted medicines for solid tumors.

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The funding round was led by OrbiMed with co-leads Novo Holdings and Jeito Capital. New investors Frazier Life Sciences, Longitude Capital, Catalio Capital, Piper Heartland Healthcare Capital and Avego Bioscience Capital participated in the round. Significant backing was also received from existing investor RA Capital Management, along with support from Morningside Venture Investments, BB Pureos, Bpifrance through its InnoBio 2 fund, as well as other early institutional investors, all of whom have been instrumental to Alentis’ development path.

"This financing is a testament to the transformational potential of CLDN1 antibody-drug conjugates (ADCs) for the treatment of solid tumors," said Roberto Iacone, Chief Executive Officer of Alentis. "Let me take this opportunity to extend a warm welcome to our new investors." Dr. Iacone added, "We’re excited to execute our development strategy and deliver clinical data for our programs over the next 12-18 months."

The proceeds of the financing will be used to conduct Phase 1/2 clinical trials of two first-in-class ADCs targeting CLDN1, ALE.P02 and ALE.P03, further development of the pipeline, and general corporate purposes.

The FDA recently cleared an IND application for a Phase 1/2 clinical trial of ALE.P02 (with a tubulin inhibitor) in advanced or metastatic CLDN1+ squamous solid tumors. The clinical trial is expected to commence Q1 2025. For ALE.P03 (with a topoisomerase I inhibitor), a first-in-human trial in patients with CLDN1+ tumors is planned to start in 2025.

Luca Santarelli, Chairman of Alentis said, "I am excited about the future of Alentis, especially after this very significant financing, and would like to welcome the new Board Members that will join after the closing of the transaction."

OrbiMed Partner, Dina Chaya said, "With this financing, Alentis is now well positioned to advance its CLDN1 antibody-drug conjugates, which have the potential to be first and best-in-class therapies for the treatment of cancer."

"ADCs have shown their potential to be highly effective cancer treatments," said Naveed Siddiqi, Senior Partner at Novo Holdings, Venture Investments. "Alentis has an exciting pipeline of first-in-class ADCs and we are proud to have co-led this round. We are looking forward to seeing the data generated from the first clinical trials of ALE.P02 and ALE.P03."

Dr. Rafaèle Tordjman, Founder and CEO of Jeito Capital said, "We are excited to co-lead this major new financing round for Alentis that further validates the strength of its pipeline. We look forward to continuing to bring our expertise to support their development."

New Board of Directors Appointments
As part of the financing, three new Board Members will join the Alentis Board of Directors, further strengthening the business, science and drug development expertise at the Board level.

Dina Chaya, Partner at OrbiMed, has over 20 years of experience in healthcare investments, specializing in biopharma and medical technology.
Anna Chen, Principal at Frazier Life Sciences, where she has been involved with investing in and building many of Frazier Life Sciences’ biopharmaceutical portfolio companies over the past 7 years.
Brian Liu, Managing Director at Longitude Capital, brings more than 10 years of biopharma consulting and investing experience, focusing on transformative healthcare innovation.
About ALE.P02 and ALE.P03
ALE.P02 and ALE.P03 are first-in-class ADCs designed by linking a potent cancer drug (a tubulin and topoisomerase I inhibitor, respectively) to our antibody that specifically targets a unique CLDN1 epitope exposed on cancer cells. This combination creates a powerful new tool to fight cancer with less toxicity than traditional cancer drugs. The IND application for ALE.P02 to commence a Phase 1/2 clinical trial in advanced or metastatic CLDN1+ squamous solid tumors was recently cleared by the FDA.