On October 6, 2022 Nested Therapeutics, a biotechnology company pioneering a next-generation precision medicine platform to address hard-to-treat cancers, reported the completion of a $90 million Series A financing led by the Life Sciences Investing business within Goldman Sachs Asset Management, bringing the total financing to $125 million since Versant Ventures founded the company (Press release, Nested Therapeutics, OCT 6, 2022, View Source [SID1234621779]). New investors participating in the Series A include Foresite Capital, Avidity Partners, Cowen Healthcare Investments, and Section 32.

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!

The financing will enable Nested to advance its pipeline programs, attract additional top-tier talent, and further develop its platform that reveals cryptic, or newly uncovered, driver mutations and pockets in high-conviction cancer targets to dramatically expand the reach of precision medicine.

"Our drug discovery platform enables us to find new, overlooked areas of opportunity in the form of high confidence targets with unconventional pockets, while also generating the insights necessary to design therapeutics with novel mechanisms for a perfect fit," said Darrin Miles, Chief Executive Officer of Nested Therapeutics. "Patients deserve more and better options, and our approach holds the promise to make first- and best-in-class precision oncology treatments available to a larger addressable population."

A Differentiated Oncology Platform
Nested’s platform involves a three-pillar approach that: (1) maps mutational clusters onto the structural proteome, (2) identifies druggable pockets and cancer-driving mechanisms, and (3) designs novel drugs optimized for the druggable pocket. The company’s lead compound, NEST-1, is a non-degrading dual molecular glue that targets multiple components of the MAPK pathway and has demonstrated potentially superior efficacy, tolerability and CNS activity relative to both single agents and combinations in RAS/MAPK-driven models.

"Working closely with our scientific co-founders and advisory board, we recognized the limitations with current precision medicines and felt there was an opportunity to combine insights and expertise from our various fields to build more effective therapies," said Klaus Hoeflich, Ph.D., Co-Founder and Chief Scientific Officer at Nested. "Our platform uses insights from an array of fields, including genomics, structural biology, computational biophysics, and artificial intelligence. This opens doors to design novel small molecules for previously known targets with well-understood biology and to target what has been previously undruggable."

"Nested Therapeutics is poised to dramatically increase the number of targets that can be reached through precision medicine, giving more patients an opportunity to be treated with better, more targeted therapies," said Josh Richardson, M.D., Managing Director at Goldman Sachs Asset Management. "We look forward to working with this impressive team of industry experts to support the development of their platform and pipeline of medicines."

Nested Leadership Team
Nested is led by a highly experienced team of pioneers in the precision medicine space who have collectively brought 35 molecules to the clinic and overseen 10 precision oncology medicines now on the market, including:

Darrin Miles, Chief Executive Officer
Darrin brings invaluable experience in leading biotech program strategy and development and successfully overseeing novel cancer therapies through approval and commercialization. Darrin has held leadership roles at Agios Pharmaceuticals, where he was Chief Commercial Officer and previously led the precision oncology program management function through the development and approval of IDHIFA and TIBSOVO. He also spent 14 years at Genentech in numerous roles including leading global program strategy and US commercialization efforts for multiple brands, including Herceptin, Perjeta and Tarceva, among others.
Klaus Hoeflich, Ph.D., Co-Founder and Chief Scientific Officer
Dr. Hoeflich brings twenty years of R&D experience of small molecule drug discovery to the team. Prior to Nested, Dr. Hoeflich served as Senior Vice President of Biology at Blueprint Medicines, using expertise in protein kinases to advance precision therapies for genomic cancers, immuno-oncology, and rare diseases. He also worked at Genentech, where his team helped advance several programs into clinical development, including the approval of Cotellic for metastatic melanoma.
Yongxin Han, Ph.D., Head, Drug Discovery
Dr. Han has led multiple teams in the discovery and advancement of twelve development candidates in oncology, immune-oncology, chronic HIV and HCV infections, pain and inflammation, metabolic disorders, hypertension, and glaucoma. Before joining Nested, Dr. Han spent more than 27 years at Merck Research Laboratories where he served as a respected mentor, authored and co-authored over fifty-five publications in peer reviewed journals, and invented and co-invented more than seventy patents.
Nested Scientific Founders and Advisors
The team is bolstered by a scientific advisory board with deep expertise in precision medicine, computational chemistry, biophysics, and proteomics, including:

Kevan Shokat, Ph.D., Scientific Co-founder
Dr. Shokat is an Investigator at the Howard Hughes Medical Institute, Professor in the Department of Cellular and Molecular Pharmacology at UCSF and a Professor of Chemistry at UC Berkeley. His lab is most well-known for drugging the "undruggable" oncogene K-Ras in 2013, leading to the development of the drug sotorasib which was approved for the treatment of lung cancer patients with the K-Ras mutation.
Arvin Dar, Ph.D., Scientific Co-founder
Dr. Dar is a Professor in the Departments of Oncological Studies and Pharmacological Sciences at the Icahn School of Medicine at Mount Sinai, as well as Associate Director of the Mount Sinai Center for Therapeutic Discovery. His groundbreaking research has earned him numerous awards and recognition, including the NIH Director’s New Innovator Award, Damon-Runyon Rachleff Innovation Award, the Pew Charitable Trusts Pew-Stewart Scholarship for Cancer Research, among others.
Ryan Corcoran, M.D., Ph.D.
Dr. Corcoran currently serves as the Director of the Gastrointestinal Cancer Center Program and the Scientific Director of the Termeer Center for Targeted Therapy at the Massachusetts General Hospital Cancer Center. Ryan directs a research laboratory focused on personalized cancer medicine: the development of therapeutic strategies that target the specific mutations driving individual patients’ tumors. Dr. Corcoran is also a co-founder of Alterome Therapeutics and serves on the Scientific Advisory Board for C4 Therapeutics, Remix Therapeutics, Cogent Biosciences, among others.
Cigall Kadoch, Ph.D.
Dr. Kadoch is an Associate Professor of Pediatric Oncology at the Dana-Farber Cancer Institute and Harvard Medical School, Institute Member and Epigenomics Program Co-Director at the Broad Institute of MIT and Harvard, and Investigator of the Howard Hughes Medical Institute. She is also the Scientific Founder of Foghorn Therapeutics. She is a leading expert in chromatin and gene regulation and is internationally recognized for her groundbreaking studies in these areas.
Tarun Kapoor, Ph.D.
Dr. Kapoor is the Pels Family Professor and head of the Selma and Lawrence Ruben Laboratory of Chemistry and Cell Biology at The Rockefeller University. His lab studies the molecular mechanisms required for accurate propagation of genetic material during cell division, with the goal of developing new therapies to treat cancer. Additionally, he is a faculty member with the David Rockefeller Graduate Program and the Tri-Institutional Ph.D. Program in Chemical Biology, where he also serves as Program Co-Director.
Angela Koehler, Ph.D.
Dr. Koehler is the Kathleen and Curtis Marble Professor in the Department of Biological Engineering at MIT and an Associate Director of the David H. Koch Institute for Integrative Cancer Research at MIT. Koehler’s Lab aims to innovate in the earliest stages of drug discovery by building chemical tools or technologies to assist in the process of target validation and by expanding the repertoire of protein targets that are considered to be druggable.
"The team at Nested is an incredibly dedicated group working to advance precision medicine towards a variety of challenging yet unequivocal targets in cancer," said Arvin Dar, Ph.D., scientific co-founder and observing member of the Board of Directors at Nested Therapeutics. "My fellow co-founder, Kevan, and I are honored that this talented group of drug hunters are building from science in our respective labs and are optimistic about what they have accomplished in a relatively short amount of time."

"We have seen tremendous progress in precision medicine over the past several decades, but there continue to be barriers to drugging the wide array of genetically validated oncology targets," said Carlo Rizzuto, Ph.D., Managing Director at Versant Ventures and a Nested board member. "With Nested, our newest portfolio company in the space, we believe there now is potential to unlock significant therapeutic real estate."

On October 6, 2022 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company developing the next generation of therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported it is scheduled to provide an update on its programs at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), which will be held in Boston, MA from November 8 – 12, 2022 (Press release, Phio Pharmaceuticals, OCT 6, 2022, View Source [SID1234621778]). This will include an update on its first-in-human clinical trial with PH-762 in advanced melanoma; data demonstrating the potential of PH-762 to further enhance the function of tumor infiltrating lymphocytes (TILs) with its partner AgonOx, Inc.; and new preclinical data on relevant targets identified in cancer immunotherapy using our INTASYL compounds.

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!

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.

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!

"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]).

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!

"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.

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!

"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.