On October 6, 2022 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer, reported the initiation of the potentially pivotal Phase 2 clinical trial of ALLO-501A (ALPHA2 trial) in patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL) (Press release, Allogene, OCT 6, 2022, View Source [SID1234621775]). The Company is also in the process of initiating the EXPAND trial, which is intended to demonstrate the contribution of ALLO-647 to the standard fludarabine/cyclophosphamide lymphodepletion regimen. Assuming favorable outcomes and subject to discussions with the U.S. Food and Drug Administration (FDA), the Company expects these studies to support the regulatory approval of both ALLO-501A and ALLO-647.

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"We are proud to initiate the industry’s first potentially pivotal Phase 2 trial for an allogeneic CAR T product. This milestone paves the road for both ALLO-501A and our broader pipeline of innovative products with the potential to greatly increase patient access to cell therapy," said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. "It is a culmination of years of hard work and perseverance, which could only be accomplished in collaboration with our dedicated staff, investigators, clinical trial site coordinators, regulatory authorities and most importantly the patients who have participated in our studies."

Allogene conducted an extensive Phase 1 program designed to evaluate and optimize all aspects of AlloCAR T, including doses and schedules of ALLO-501A and ALLO-647. In addition, the Company recently conducted a review of the Phase 1 program which determined a manufacturing process associated with robust clinical performance. Allogene’s selected manufacturing process, named Alloy, will be deployed in the ALPHA2 and EXPAND trials.

Allogene received Chemistry Manufacturing and Controls (CMC) clearance to use newly manufactured product that did not utilize the Alloy process from its manufacturing facility, Cell Forge 1 (CF1). The Company is now in the process of implementing Alloy in this facility. As such, the Phase 2 trial will begin with previously manufactured material with the intent of transitioning to product from CF1 during the course of the ALPHA2 and EXPAND trials.

The single-arm Phase 2 ALPHA2 trial in r/r LBCL will utilize a single dose of ALLO-501A at 120 million CAR+ cells with an intended lymphodepletion regimen (FCA90) comprised of fludarabine (30 mg/m2/day x 3 days) and cyclophosphamide (300 mg/m2/day x 3 days) plus ALLO-647 (90 mg). The ALPHA2 trial will enroll approximately 100 patients who have received at least two prior lines of therapy and have not received prior anti-CD19 therapy. The primary endpoint is objective response rate (ORR).

The EXPAND trial is a separate potentially registrational trial for ALLO-647. Allogene is developing ALLO-647, its anti-CD52 monoclonal antibody, with the goal of potentially enabling expansion, persistence and improved clinical outcomes of AlloCAR T product candidates, including ALLO-501A. The randomized EXPAND trial is expected to enroll approximately 70 patients with r/r LBCL and is intended to demonstrate the safety of ALLO-647 and its contribution to the overall effectiveness of the lymphodepletion regimen. Patients will be randomized to receive the same single 120 million cell dose of ALLO-501A as in the ALPHA2 trial and either lymphodepletion with fludarabine and cyclophosphamide alone (control arm) or the same lymphodepletion regimen of the ALPHA2 trial (active arm).

In June, the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to ALLO-501A in r/r LBCL. RMAT designation was based on data demonstrating the potential of ALLO-501A to address an unmet need for patients with relapsed/refractory disease. Previously presented data support the potential of ALLO-501A as an alternative to approved autologous CAR T therapies. In the ALLO-501A Phase 1 study, nearly all enrolled patients were able to receive therapy with the median time from enrollment to initiation of treatment of two days.

Allogene expects to provide an update on its CD19 program toward the end of 2022. This will include longer-term follow-up from the ALPHA and ALPHA2 Phase 1 trials, including patients treated with the Alloy manufacturing technology process.

On October 6, 2022 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company developing targeted protein modulation drugs, reported financial results for the third quarter ended August 31, 2022 and provided a corporate update (Press release, Nurix Therapeutics, OCT 6, 2022, View Source [SID1234621774]).

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"The third quarter was highly productive for Nurix with continued progress in our development programs, expansion of our leadership team and the completion of significant registered direct offerings that enabled us to strengthen our balance sheet," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "We look forward to maintaining our momentum into the end of year as we continue to execute on the clinical trials of our wholly owned programs and provide important updates through the remainder of the year."

Recent Business Highlights

Strengthened the balance sheet with two registered direct offerings raising gross proceeds of $95 million: Nurix entered into two securities purchase agreements with healthcare-focused investment funds to sell, in registered direct offerings, pre-funded warrants to purchase an aggregate of 6,814,920 shares of Nurix’s common stock at a price of $13.939 per pre-funded warrant, cumulatively yielding total gross proceeds of $95 million.
Expanded the Nurix leadership team and board with the hiring of chief people officer and the appointment of leading industry strategist to the board of directors: In August, Nurix announced that industry veteran, Eric Schlezinger, J.D., joined the company as chief people officer. Mr. Schlezinger has extensive experience leading and developing human resources at high-growth private and public biopharma companies. In September, Nurix announced the appointment of leading industry strategist Edward C. Saltzman to its board of directors. Mr. Saltzman has over 30 years of drug strategic development experience and currently serves as Head of Biotech Strategy at Lumanity Inc., a global pharmaceutical and biotechnology advisory firm.
Announced acceptance of six abstracts at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting (November 8-12, 2022): Nurix will have six poster presentations at the meeting, including a presentation of initial biomarker data from the Phase 1 clinical trial of NX-1607, a first-in-class oral inhibitor of Casitas B-lineage lymphoma proto-oncogene B (CBL-B) in patients with advanced malignancies.
Upcoming Program Highlights*

NX-2127: Nurix’s lead drug candidate from its protein degradation portfolio, NX-2127, is an orally bioavailable degrader of BTK with immunomodulatory activity for the treatment of patients with relapsed or refractory B-cell malignancies. Nurix is conducting its Phase 1 clinical trial of NX-2127 at multiple clinical sites. Nurix anticipates presenting additional clinical results from the Phase 1a portion of the trial by the end of 2022. Additional information on the clinical trial can be accessed at clinicaltrials.gov (NCT04830137).
NX-5948: Nurix’s second drug candidate from its protein degradation portfolio, NX-5948, is an orally bioavailable BTK degrader designed without immunomodulatory activity for certain B-cell malignancies and autoimmune diseases. Nurix is evaluating NX-5948 in a Phase 1 clinical trial in adults with relapsed or refractory B-cell malignancies and expects to have initial PK/PD data from the Phase 1a portion of the study by the end of 2022. Additional information on the clinical trial can be accessed at clinicaltrials.gov (NCT05131022).
NX-1607: Nurix’s lead drug candidate from its targeted protein elevation portfolio, NX-1607, is an orally bioavailable inhibitor of the E3 ligase CBL-B for immuno-oncology indications including a range of solid tumor types. Nurix is evaluating NX-1607 in an ongoing, Phase 1 dose escalation and expansion trial in adults with a variety of oncology indications at multiple clinical sites and expects to present initial PK/PD data from the Phase 1a stage of the study at the SITC (Free SITC Whitepaper) 2022 annual meeting. Additional information on the clinical trial can be accessed at clinicaltrials.gov (NCT05107674).
DeTIL-0255: Nurix’s lead candidate in its cellular therapy portfolio, DeTIL-0255, is a drug-enhanced adoptive cellular therapy. Nurix is evaluating DeTIL-0255 in a Phase 1 trial in adults with gynecological malignancies including ovarian cancer, cervical cancer, and endometrial cancer. Nurix anticipates providing a clinical update from the run-in portion of the DeTIL-0255 Phase 1 study by the end of 2022. Additional information on the clinical trial can be accessed at clinicaltrials.gov (NCT05107739).
* Expected timing of events throughout the press release are based on calendar year quarters.

Fiscal Third Quarter 2022 Financial Highlights

Collaboration revenue for the three months ended August 31, 2022 was $10.8 million compared to $10.3 million for the three months ended August 31, 2021. The increase was primarily due to the continued scale up of internal resources and external spending for our collaborations with Sanofi and Gilead as compared to the prior period, resulting in a higher percentage of completion in the current period. In the three months ended August 31, 2022, Nurix achieved a research milestone under its collaboration with Gilead and anticipates a payment of $2.5 million in the fourth fiscal quarter of 2022.

Research and development expenses for the three months ended August 31, 2022 were $47.8 million compared to $30.9 million for the three months ended August 31, 2021. The increase was primarily related to an increase of $7.3 million in compensation and related personnel costs and an increase of $2.0 million in non-cash stock-based compensation expense primarily attributable to an increase in headcount. In addition, there was an increase of $5.3 million in supplies and contract research and preclinical and clinical costs due to ongoing clinical trial startup and patient enrollment and preclinical and drug discovery activities.

General and administrative expenses for the three months ended August 31, 2022 were $9.7 million compared to $8.3 million for the three months ended August 31, 2021. The increase was primarily related to an increase of $0.3 million in compensation related expenses and an increase of $0.7 million in non-cash stock-based compensation expense. There was also an increase of $0.4 million in professional service and consulting expenses.

Net loss for the three months ended August 31, 2022 was $45.7 million, or ($0.90) per share, compared to a net loss of $28.8 million for the three months ended August 31, 2021, or ($0.65) per share.

Cash, cash equivalents and marketable securities: As of August 31, 2022, Nurix had cash, cash equivalents and marketable securities of $413.6 million compared to $348.8 million as of May 31, 2022. The increase was primarily attributable to $95.0 million of gross proceeds from two registered direct offerings of pre-funded warrants to purchase Nurix common stock that were completed in July 2022.

On October 6, 2022 Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported the completion of patient enrollment in UPLIFT, the company’s single-arm registrational trial of UpRi in platinum-resistant ovarian cancer (Press release, Mersana Therapeutics, OCT 6, 2022, View Source [SID1234621773]). UpRi is Mersana’s first-in-class NaPi2b-targeting ADC with a novel scaffold-linker-payload that enables a high drug-to-antibody ratio and controlled bystander effect.

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"The completion of enrollment in UPLIFT moves us one step closer to our goal of establishing UpRi as a foundational therapy for ovarian cancer," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "Thanks in large part to the enthusiasm we have seen about UpRi among global investigators, the significant unmet needs of patients in the platinum-resistant setting and strong execution from our team, we were able to enroll more than 270 patients in this trial within approximately a year. As a result, we believe we will have a robust data set for a planned topline data readout from UPLIFT in mid-2023 and, assuming positive data, a potential U.S. Food and Drug Administration BLA submission by the end of 2023. We extend our sincere thanks to the patients, caregivers, clinical investigators and staff who are participating in UPLIFT."

UPLIFT is a single-arm clinical trial evaluating the safety and efficacy of UpRi in patients with platinum-resistant ovarian cancer who have received up to four prior lines of therapy. Patients with three or four prior lines of therapy were able to enroll in UPLIFT without regard to prior bevacizumab treatment. The trial enrolled a total of 272 patients to receive a 36 mg/m2 dose of UpRi every four weeks. While NaPi2b testing of patient tumor samples is ongoing, the company expects that it will exceed its targeted number of NaPi2b positive patients in UPLIFT. The trial’s primary endpoint is the objective response rate (ORR) in the NaPi2b positive population, and secondary endpoints include the ORR regardless of NaPi2b expression, as well as duration of objective response and incidence and severity of adverse events.

On October 6, 2022 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T-cell reprogramming company dedicated to developing curative cell therapies for patients with solid tumors, reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application to initiate a Phase 1 clinical trial for LYL845 (Press release, Lyell Immunopharma, OCT 6, 2022, View Source [SID1234621772]). LYL845 is an investigational tumor infiltrating lymphocyte (TIL) therapy enhanced with Lyell’s Epi-R technology for patients with relapsed and/or refractory metastatic or locally advanced melanoma and other select solid tumors. In preclinical studies, Epi-R creates polyclonal populations of T cells that demonstrate properties of durable stemness and anti-tumor functionality. Durable stemness is the quality that enables T cells to self-renew, proliferate, persist and generate differentiated effector cell progeny.

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LYL845 is Lyell’s first TIL product candidate and second wholly owned product candidate to receive IND clearance within the past year. Patient screening for the Phase 1 trial is set to begin over the coming months, and initial clinical data is expected in 2024.

"Advancing LYL845 into the clinic represents steady progression of our mission to develop T-cell therapies that can outlast and eradicate solid tumors," said Liz Homans, chief executive officer of Lyell. "Our goal is to develop LYL845 as an effective TIL therapy for patients with solid tumor cancers such as melanoma, as well as for indications where TIL therapy has not yet been widely effective such as non-small cell lung and colorectal cancer."

"We have developed our epigenetic reprogramming technology to produce T-cell populations with more favorable attributes than those generated by standard manufacturing approaches," stated Rick Klausner, MD, chair of Lyell’s Board of Directors. "LYL845 T cells are highly polyclonal and exhibit qualities of durable stemness that have been linked with the anti-tumor functionality and improved outcomes in previous TIL clinical trials, and we look forward to clinically evaluating LYL845 and the role of these qualities in cell therapy for solid tumors."

"While TILs have previously shown clinical benefit in patients with melanoma and limited other solid tumors, we believe that TIL with properties of durable stemness and increased polyclonality are needed for adoptive cell therapies to have curative potential," said Tina Albertson, MD, PhD, chief medical officer and head of development of Lyell.

Phase 1 Trial Design

The Phase 1 clinical trial is an open-label, dose-escalation trial for patients with relapsed and/or refractory metastatic or locally advanced melanoma with expansion cohorts for patients with melanoma, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). The primary objective of the trial is to determine safety, tolerability and a recommended phase 2 dose range of LYL845. The secondary objective is to determine antitumor activity as evaluated by response rates, duration of response, progression free survival and overall survival. Exploratory biomarkers of T-cell stemness will also be assessed.

About Melanoma, NSCLC and CRC

Melanoma accounts for only ~1% of all skin cancers but is responsible for ~80% of skin cancer-related deaths. Only ~14% of patients with metastatic melanoma survive for five years.

Lung cancer is the second most common cancer and is the leading cause of cancer mortality worldwide. NSCLC accounts for 84% of all lung cancers. For localized NSCLC, the overall 5-year survival rate is ~60%. For regional NSCLC, the 5-year survival rate is ~35%. Based on current data, when NSCLC metastasizes, the 5-year survival rate is 6%.

Colorectal cancer is the second most common cause of cancer deaths in the United States. For localized CRC, the overall 5-year survival rate is ~90% but for metastatic disease, the 5-year survival rate is 14%. Approximately 25% of patients have metastatic disease at diagnosis, and ~50% of patients with colorectal cancer will eventually develop metastases.

About LYL845

LYL845 is an autologous tumor infiltrating lymphocyte (TIL) product candidate enhanced with Epi-R reprogramming technology for patients with relapsed and/or refractory metastatic or locally advanced melanoma and select solid tumors. In preclinical studies, Epi-R creates polyclonal populations of T cells that demonstrate properties of durable stemness and anti-tumor functionality. Durable stemness is the quality that enables T cells to self-renew, proliferate, persist and generate differentiated effector cell progeny.

TIL products are created by expanding T cells taken from the patient’s own tumor. Previous clinical experiences suggest that the efficacy of adoptive transfer of ex vivo expanded TILs is largely driven by specific recognition of mutated tumor neoantigens specific to each patient. To date, broad efficacy of TIL therapies has been limited by variable and often poor product quality, lack of stemness or potential durability of expanded TILs, failure to maintain polyclonality of TILs during production, and failure to enrich the TIL product with tumor-reactive T cells.

TIL products manufactured using Lyell’s Epi-R reprogramming technology aim to overcome these challenges. Preclinical studies supporting the development of LYL845 suggest Epi-R technology improves TIL products by maintaining properties of durable stemness, which leads to superior ex vivo cell expansion and product qualities, maintenance of tumor reactive clones, and enhanced polyclonality.

On October 6, 2022 Surrozen, Inc. (Nasdaq: SRZN) reported that it has entered into a collaboration and license agreement with Boehringer Ingelheim to research and develop SZN-413 for the treatment of retinal diseases (Press release, Boehringer Ingelheim, OCT 6, 2022, View Source [SID1234621771]).

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SZN-413 is a bi-specific antibody targeting Fzd4-mediated Wnt signaling designed using Surrozen’s SWAP technology. It is currently being developed for the treatment of retinal vascular-associated diseases. Data generated by Surrozen with SZN-413 in preclinical models of retinopathy demonstrated that SZN-413 could potently stimulate Wnt signaling in the eye, induce normal retinal vessel regrowth, suppress pathological vessel growth and reduce vascular leakage (doi: View Source). This novel approach could thus potentially allow for regeneration of healthy eye tissue, not only halting retinopathy, but possibly allowing for a full reversal of the patient’s disease.

Under the terms of the agreement, Boehringer Ingelheim will receive an exclusive, worldwide license to develop SZN-413 and other Fzd4-specific Wnt-modulating molecules for all purposes, including as a treatment for retinal diseases, in exchange for an upfront payment to Surrozen of $12.5 million. Surrozen will also be eligible to receive up to $586.5 million in success-based development, regulatory, and commercial milestone payments, in addition to mid-single digit to low-double digit royalties on sales. After an initial period of joint research, Boehringer Ingelheim will assume all development and commercial responsibilities.

"Surrozen looks forward to the new partnership with Boehringer Ingelheim and to having our teams and scientists work to advance the potential opportunities for our Fzd4-targeted Wnt agonist program. We believe that compelling genetic and experimental evidence of the role for Fzd4-specific Wnt signaling in retinal vascular function points to the potential clinical impact of our approach. Boehringer Ingelheim is the optimal partner to translate that evidence into potential breakthrough therapies to transform the lives of people with retinal diseases," said Craig Parker, Chief Executive Office at Surrozen.