On November 11, 2021 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in cell therapy to treat cancer, reported that it will report updated clinical and translational data from its pivotal SPEARHEAD-1 trial with afamitresgene autoleucel (afami-cel, formerly ADP-A2M4) in patients with advanced synovial sarcoma or myxoid/round cell liposarcoma (MRCLS) at the Connective Tissue Oncology Society (CTOS) annual meeting (Press release, Adaptimmune, NOV 11, 2021, View Source [SID1234595287]).

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"The positive results presented at CTOS further validate the potential of this therapy to address a great unmet medical need for patients with synovial sarcoma and MRCLS," said Elliot Norry, Adaptimmune’s Chief Medical Officer. "We are confident that these data will support our BLA filing for afami-cel next year."

"Afami-cel would provide a new treatment option for patients with synovial sarcoma, offering benefits that we have rarely seen with therapies currently available for this patient population," said Dr. Brian A. Van Tine, Professor of Medicine and of Pediatrics at Washington University School of Medicine in St. Louis. "This is a game changer for patients with a high unmet medical need."

Clinical data will be presented in an oral presentation by Dr. Brian Van Tine of the Washington University School of Medicine in St. Louis (Abstract #1080870) during the Immunotherapy & Immune Microenvironment Session starting at 10:00 a.m. EST on November 12th.

Preliminary translational insights from the Phase 2 SPEARHEAD-1 trial will also be presented in a poster (Abstract #1080366) by Dr. Sandra P. D’Angelo of Memorial Sloan Kettering Cancer Center during the Immunology & Immunotherapy Session beginning at 2:30 p.m. EST on November 12th.

Efficacy data validate the meaningful clinical benefit of afami-cel (data cut-off September 1, 2021)

50 patients had received afami-cel (42 with synovial sarcoma, 8 with MRCLS)
Median age of patients was 41 years (range: 19 to 73) and they had received a median of three prior lines of therapy (range: 1 to 12)
The median dose was 8.5 billion transduced SPEAR T-cells (range: 2.7 to 10)
Three patients had scans awaiting Independent Review and 47 patients were evaluable
The primary endpoint for SPEARHEAD-1 is response according to RECIST v1.1 evaluated by Independent Review 1
Based on the reported overall response rate, the trial will meet its primary endpoint in the final analysis planned later this year
Per Independent Review, the overall response rate was 34% (16/47 patients with partial responses [PRs])
The overall response rate was 36% in patients with synovial sarcoma, and 25% for patients with MRCLS
The disease control rate (defined as stable disease, PR, or CR) was 85% per Independent Review
The overall response rate and disease control rate per Independent Review were comparable to the assessments by Investigator Review (34% and 84%, respectively)
Durability is encouraging and the median duration of response has not been reached
75% of patients with response remain ongoing and the duration ranged from 4.3+ to 65.3+ weeks
Afami-cel was well-tolerated and has a favorable benefit:risk profile as of data cut-off

Thirty-three (66%) patients experienced adverse events of cytokine release syndrome (CRS), most of which were lower grade: Grade 1 or 2 (n=32); Grade 3 (n=1)
The most common serious adverse event (SAE) of any grade was CRS reported in 6% of patients
Eight (16%) patients experienced ≥ Grade 3 cytopenia at Week 4

Emerging translational data support clinical benefit seen in patients with afami-cel

Afami-cel SPEAR T-cells successfully engrafted in all patients and maintained high levels of persistence in most patients followed for at least 6 months post-infusion
CD8+ SPEAR T-cells in drug products administered killed >70% tumor cells in vitro
Serum cytokine response profile indicates an IFNγ-driven mechanism of action, signaling an afami-cel induced immune response
Clinical benefit seen across a broad range of MAGE-A4 expression
Post-infusion biopsies indicated that infiltrating afami-cel SPEAR T-cells co-localize with tumor and additional immune cells, with evidence of activated and proliferative state and adaptive-immune response
Conclusion from the Phase 2 SPEARHEAD-1 trial

The trial will meet its primary endpoint for efficacy for this pivotal trial
As of September 1, 2021, overall response rate was 34% with a disease control rate of 85% per Independent Review in 47 heavily pre-treated patients
Durability of responses is encouraging, and the median duration of response has not been reached
The benefit:risk profile of afami-cel has been favorable, with mainly low-grade CRS and tolerable/reversible hematologic toxicities
Translational data confirm that afami-cel is active against MAGE-A4 expressing targets both in vitro and in vivo
These data will be used to support Adaptimmune’s Biologics License Application (BLA) submission next year
Overview of SPEARHEAD-1 trial design
SPEARHEAD-1 is a Phase 2, open-label trial for people with advanced synovial sarcoma or MRCLS to evaluate the efficacy, safety, and tolerability of afami-cel. Afami-cel SPEAR T-cells target MAGE-A4+ tumors. MAGE-A4 is highly expressed in synovial sarcoma and MRCLS in the context of HLA-A*02. Compelling clinical responses in patients with synovial sarcoma were previously reported with afami-cel in a Phase 1 trial (CTOS 2020).

Approximately 90 patients are planned to be treated: 45 in Cohort 1 and 45 in Cohort 2. Enrollment in Cohort 1 is complete, and Cohort 2 is currently recruiting. The primary efficacy analysis will be for Cohort 1 only, which will be used to support the BLA filing next year. No formal hypothesis testing is planned for Cohort 2. Cohort 2 will strengthen the efficacy and safety database and will aid in descriptive sub-group analyses.

Key eligibility criteria: ECOG performance status of 0 or 1; HLA*02 positive with MAGE-A4 expression in ≥ 30% of tumor cells ≥ 2+ by immunohistochemistry; aged ≥ 16 and ≤ 75 years; and patients must have received either an anthracycline- or ifosfamide-containing regimen. Eligible patients received afami-cel doses between 1–10 × 109 transduced T-cells after receiving lymphodepleting chemotherapy.

On November 11, 2021 Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to cures for cancer and other serious diseases, reported that completed a Type B Pre-Biologics License Application (BLA) meeting with the U.S. Food and Drug Administration (FDA) for omidubicel, a potentially life-saving treatment for patients with blood cancers in need of stem cell transplant (Press release, Gamida Cell, NOV 11, 2021, View Source [SID1234595304]). The FDA requested that Gamida Cell provide revised analysis of the manufacturing data generated at Gamida Cell’s wholly-owned commercial manufacturing facility to demonstrate the comparability to the omidubicel that was produced at the clinical manufacturing sites for the Phase 3 study. The FDA did not request additional clinical data to initiate the BLA submission once analytical comparability is demonstrated. The company will continue to work collaboratively with the FDA and anticipates submitting the BLA in the first half of 2022 in lieu of the company’s previous plan to submit the BLA by the end of 2021.

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"Despite the delay in timing to bring omidubicel to patients after a potential FDA approval, we are encouraged by the FDA’s reaction to our Phase 3 data as the pivotal trial of omidubicel. We have gained further clarity with the FDA on the requirements for demonstrating comparability for our commercial manufacturing facility," said Julian Adams, Ph.D., Chief Executive Officer of Gamida Cell. "With the FDA’s feedback in hand, we believe that we are one step closer for omidubicel to be made available to patients in need."

Omidubicel, an investigational advanced cell therapy for allogeneic bone marrow transplant

Omidubicel is the foundational product based on Gamida Cell’s proprietary NAM-enabled cell expansion technology. It is the first cell therapy for bone marrow transplant to receive Breakthrough Therapy Designation from the FDA. The BLA submission will be based on the results of an international, randomized Phase 3 study of omidubicel that was designed to evaluate the safety and efficacy of omidubicel in patients with hematologic malignancies undergoing a bone marrow transplant compared to patients who received a standard umbilical cord blood transplant. The study achieved its primary endpoint, a statistically significant reduction in time to neutrophil engraftment, as well as all key secondary endpoints. A key milestone in a patient’s recovery, neutrophil engraftment is a measure of how quickly the stem cells a patient receives in a bone marrow transplant are established and begin to make healthy new cells. In the Phase 3 study, the median time to neutrophil engraftment was 12 days for patients randomized to omidubicel compared to 22 days for the comparator group (p < 0.001). Additionally, the study met key secondary endpoints related to the speed of platelet engraftment, decrease in infections and reduction in hospitalizations, all significant clinical measures in bone marrow transplant.

On November 11, 2021 Acrivon Therapeutics, Inc., a clinical-stage oncology therapeutics company with proprietary technologies driving a new era of precision-based medicine, reported the successful completion of an oversubscribed $100 million Series B financing (Press release, Acrivon Therapeutics, NOV 11, 2021, View Source [SID1234595330]). The financing was co-led by Wellington Management Company and Surveyor Capital (a Citadel company), with key participation from RA Capital Management and Perceptive Advisors. Additional new investors in the financing included Sands Capital, HBM Healthcare Investments, Marshall Wace, HealthCor Management, BB Pureos Bioventures, Acorn Bioventures, and existing investors, including Alexandria Venture Investments and Chione Ltd. In connection with the financing, Derek DiRocco, Ph.D., partner at RA Capital Management, will join the company’s Board of Directors.

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Acrivon’s Predictive Precision Proteomics (AP3) technology platform enables the development of drug-tailored OncoSignature companion diagnostics that link drug mechanisms to the active disease-driving processes of cancer in patients, uncovering drug sensitivity not achievable through traditional genomics analyses. Acrivon’s pipeline will be advanced in clinical trials selectively enrolling patients predicted to benefit from treatment based on its proprietary OncoSignature companion diagnostics. The company’s clinically advanced lead product candidate ACR-368 (also known as prexasertib, in-licensed from Eli Lilly and Company) is a potent, second generation CHK1/2 inhibitor which has shown durable, single-agent anticancer activity, including complete responses, in a proportion of patients across multiple cancers in Phase 2 studies.

"On the heels of the company’s recent public launch in late June, we are pleased to have attracted a top-tier syndicate of leading private/public investors that recognize the transformative potential of our platform and pipeline," said Peter Blume-Jensen, M.D., Ph.D., chief executive officer and founder of Acrivon. "Appropriate patient selection is one of the biggest unmet needs for targeted oncology therapeutics and is currently not possible for the majority of common solid cancers. We are excited to now leverage the broader potential of our AP3 platform, which enables us to decipher a drug’s true mechanism-of-action at high resolution and accurately match that with the disease-driving processes in a patient’s tumor. This allows us to not only predict individual patient response, but also identify new indications and rational drug combinations, as well as hurdles that block patient responses, such as resistance mechanisms. The initial application of our technology is for the development of ACR-368 and two other undisclosed pipeline programs targeting solid tumors."

Derek DiRocco, Ph.D., partner at RA Capital and member of the board added, "Acrivon’s lead asset ACR-368 has demonstrated impressive monotherapy activity in several cancers, and the late-stage Phase 2 development strategy using their proprietary patient selection methodology can lead to multiple accelerated approval opportunities in these high unmet need cancers. We are impressed by the company’s foundational technologies and believe they are broadly applicable to therapeutics beyond ACR-368 and have the potential to usher in a new era of precision-based medicine beyond the industry’s current approaches, which are largely limited to the use of genomic biomarkers."

"We are thrilled by the support from these notable investors," said Kristina Masson, Ph.D., co-founder and site head of Acrivon AB, Acrivon’s phospho-proteomic and drug discovery hub located in Medicon Village, Lund, Sweden. "We have strategically built our phospho-proteomics capabilities here to leverage the proximity to our academic co-founder, professor Jesper Olsen at the University of Copenhagen, Denmark, who is a recognized leader in the field of phospho-proteomics. Likewise, our structure-guided drug discovery programs benefit from local expertise in structural biology and medicinal chemistry. The excellent infrastructure and world-leading proteomics expertise established at our hub in Scandinavia remains a major competitive advantage for Acrivon, and we are excited to also welcome several European investors to join our investor syndicate."

About Acrivon Precision Predictive Proteomics
Acrivon Predictive Precision Proteomics, AP3, is a proprietary, streamlined approach to develop patient selection tumor biopsy tests, called OncoSignature tests. The technology is engineered to be agnostic to underlying genetic alterations and enables identification and treatment of the patients whose tumors are regulated by and sensitive to the drug based on direct protein measurement of the critical tumor-driving mechanisms. The AP3 approach leverages unbiased differential global phosphoproteomic drug profiling using mass spectrometry, biased tumor model analyses, and quantitative multispectral in situ imaging of patient derived xenograft (PDX) in vivo models and intended-use tumor samples and clinical trial biopsies, to identify and evaluate biomarkers. The output of AP3 is clinically actionable, drug-tailored, proprietary OncoSignature tests. These are automated, quantitative protein multiplex imaging tests applied to pretreatment tumor biopsies as a companion diagnostic (CDx) to select and treat the patients predicted to benefit from the drug. The AP3 method is broadly applicable across drugs and is a transformative, efficient method to accurately match the right therapy to the right patient.

About ACR-368 (also known as prexasertib)
ACR-368 is a potent, selective inhibitor of CHK1 and CHK2 which has shown deep durable single agent activity, including complete responses, in a proportion of patients across several Phase 2 studies of platinum-resistant ovarian cancer and in squamous cell cancers, including anal cancer for which FDA has granted orphan drug designation. ACR-368 has been tested in >1,000 patients as monotherapy and in combination, showing excellent pharmacokinetic and pharmacological properties and a favorable safety profile at the recommended Phase 2 dose across monotherapy studies. Acrivon has obtained exclusive, world-wide rights to develop and commercialize ACR-368 under a license agreement with Eli Lilly and Company.

On November 11, 2021 Immunocore (Nasdaq: IMCR), a late-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, infectious and autoimmune disease, reported that management will participate in a fireside chat at the Jefferies London Healthcare Conference, taking place November 16-19, 2021 (Press release, Immunocore, NOV 11, 2021, View Source [SID1234595191]).

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The presentation will be available on-demand for attendees during the virtual conference beginning on November 18, 2021. The webcast can also be accessed in the ‘Investors’ section of Immunocore’s website at www.immunocore.com.

On November 11, 2021 Obsidian Therapeutics, Inc., a biotechnology company pioneering engineered cell and gene therapies, reported that Company management will participate in three upcoming investor conferences and include an update on progress with its OBX-115 program (Press release, Obsidian Therapeutics, NOV 11, 2021, View Source [SID1234595254]):

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Jefferies Global Healthcare Conference (London) |Presenting onTuesday, November 16, 2021 at 9:20 a.m. GMT | View Source
Piper Sandler 33rd Annual Virtual Healthcare Conference |Presentations will be available for registered attendees from Monday, November 22, 2021 at 10:00 a.m. ET through December 2, 2021
RBC Capital Markets Healthcare Private Company Conference | Presenting on Wednesday, December 15, 2021 at 3:50 p.m. ET
About OBX-115

OBX-115 is Obsidian’s lead cytoTIL15 program, currently in preclinical development for the treatment of patients with metastatic melanoma and other solid tumors. OBX-115 is a novel engineered tumor infiltrating lymphocyte therapy armed with regulated membrane-bound IL15 that is designed to remove the need for concomitant IL2 therapy, a toxic and costly requirement for conventional TILs. The Company expects to submit an IND for OBX-115 in mid-2022.