MapKure, BeiGene and SpringWorks Present Clinical Data on BGB-3245, a Selective Next-Generation B-RAF Inhibitor, in Adult Patients with Advanced or Refractory Solid Tumors at the American Association for Cancer Research Annual Meeting 2023

On April 17, 2023 MapKure, LLC, BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), and SpringWorks Therapeutics, Inc. (NASDAQ: SWTX), reported that they will present updated clinical data from the Phase 1a/1b study of BGB-3245, an investigational, selective RAF dimer inhibitor, in adult patients with advanced or refractory solid tumors harboring MAPK pathway aberrations (Press release, BeiGene, APR 17, 2023, View Source [SID1234630141]). The data are being presented today in an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, taking place in Orlando, Florida.

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"The promising data we are sharing at AACR (Free AACR Whitepaper) demonstrate the value of our next-generation RAF dimer inhibitor, BGB-3245, as a monotherapy in patients with MAPK pathway-altered cancers, especially its potential to address key primary and resistance gene alterations that are currently unaddressed by approved therapies," said Lusong Luo, Ph.D., Acting CEO of MapKure and Senior Vice President, External Innovation at BeiGene. "We believe that our early clinical data supported the advancement into our selected expansion cohorts which are now underway."

"SpringWorks is committed to developing genomically-targeted therapies for patients with cancer and our MAPK directed portfolio is a cornerstone of our efforts. In particular, we are encouraged by the promising activity BGB-3245 is showing in patients with MAPK pathway aberrations," said Saqib Islam, CEO of SpringWorks. "We and our partners are excited by the advancement of this program and are eager to continue making strides to benefit patients in significant need of new therapeutic options."

Oral Presentation at the 2023 AACR (Free AACR Whitepaper) Annual Meeting:

A first-in-human, phase 1a/1b, open-label, dose-escalation and expansion study to investigate the safety, pharmacokinetics, and antitumor activity of the RAF dimer inhibitor BGB-3245 in patients with advanced or refractory tumors

Presenter: Alison M. Schram, M.D., Memorial Sloan Kettering Cancer Center in New York
Session Title: Mini-symposium Session CTMS02 – Targeting the KRAS Pathway in the Clinic
Abstract #: CT031
Session Date and Time: Monday, April 17, 2023, from 3:20-3:30 PM ET

This ongoing Phase 1a/1b trial (NCT04249843) is an open-label, dose escalation and expansion study of BGB-3245 in adult patients with advanced or refractory solid tumors harboring MAPK pathway alterations. Results from the Phase 1a dose-escalation and dose-finding study are being presented at AACR (Free AACR Whitepaper). This portion of the study was designed to evaluate the safety, pharmacokinetics, preliminary antitumor activity of BGB-3245, and to determine its maximum tolerated dose and/or recommended Phase 2 dose to be used in select expansion cohorts.

As of the data cut-off of September 1, 2022, 42 patients were treated across six dose levels (5-60 mg daily). Patients were heavily pre-treated, having received a median three prior lines of therapy (range 1-9), including standard of care immunotherapy and targeted therapy regimens. Results demonstrated that BGB-3245 had a manageable safety profile, with adverse event findings consistent with other MAPK pathway inhibitors. The most common treatment-related adverse events (>15%) were rash acneiform (33%), rash maculopapular (24%), and fever (17%). The 40 mg once daily dose was determined to be the maximum tolerated dose of BGB-3245. In addition, encouraging anti-tumor activity was observed in heavily pretreated patients, with an objective response rate of 18% (6 confirmed responses including one complete response in 33 efficacy evaluable patients). The disease control rate was 79% and clinical benefit rate was 42%. Objective responders include patients with tumors harboring BRAF V600E that had progressed on prior BRAF/MEK inhibitors with or without checkpoint inhibitor treatment, BRAF Class II mutation, BRAF fusion, NRAS and KRAS mutations. Median time on treatment was approximately 5 months (range: 1.9-23.6 months) and 9 patients remain on treatment. These data supported the advancement of BGB-3245 into the Phase 1b dose expansion portion of the study, which has been enrolling patients since October 2022 in defined cohorts.

"These data support the ongoing investigation of BGB-3245 in defined cohorts, including BRAF V600 tumors that have progressed after prior BRAF and/or MEK inhibitor treatment, solid tumors with BRAF class II mutations and BRAF fusions, and NRAS mutant melanoma," said Alison M. Schram, M.D., Assistant Attending Physician at Memorial Sloan Kettering Cancer Center in New York. "These patients have very limited treatment options and I look forward to the further development of BGB-3245 as it continues to advance through the dose expansion cohorts."

About BGB-3245

BGB-3245 is an investigational, oral, selective small molecule inhibitor of RAF monomer and dimer forms. Preclinical data demonstrate that BGB-3245 has activity in tumor models that have BRAF/MEK inhibitor-resistance mutations, suggesting BGB-3245 could provide a therapeutic option for patients who have progressed on prior BRAF and/or MEK inhibitions. In addition, BGB-3245 has shown activity in preclinical models that have BRAF class II/III mutations, fusions, and splice isoforms, for which approved BRAF inhibitors are ineffective. These mutations and fusions have been identified in several solid tumors to be drivers of cancer growth, including in melanoma, non-small cell lung cancer, colorectal cancer, thyroid cancer, and other cancers.

In addition to its development as a monotherapy in several genetically defined solid tumor types, a Phase 1/2a combination study of BGB-3245 and mirdametinib is ongoing (NCT05580770) and BGB-3245 also has the potential to be used in rational combination therapies in the future.

BeiGene and SpringWorks Present Clinical Data on Lifirafenib, in Combination with Mirdametinib, in Patients with Advanced or Refractory Solid Tumors with MAPK Pathway Aberrations at the American Association for Cancer Research Annual Meeting 2023

On April 17, 2023 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), and SpringWorks Therapeutics, Inc. (NASDAQ: SWTX), reported that they will present updated clinical data from the Phase 1b trial of BeiGene’s RAF dimer inhibitor, lifirafenib, in combination with SpringWorks’ MEK inhibitor, mirdametinib, in patients with advanced or refractory solid tumors with RAS mutations, RAF mutations and other MAPK pathway aberrations (Press release, BeiGene, APR 17, 2023, View Source [SID1234630140]). The data are being presented today in an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, taking place in Orlando, Florida.

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"The lifirafenib plus mirdametinib combination represents a novel targeted approach to treat solid tumors driven by RAS/RAF mutations, and other MAPK pathway aberrations. The early clinical data reported here demonstrate the potential of this vertical combination strategy in addressing the substantial unmet medical need represented by patients with tumors driven by these genetic alterations." said Lusong Luo, Ph.D. Senior Vice President, External Innovation at BeiGene. "We are very excited about our continued study of this combination with its advancement into dose expansion this year."

"We are pleased by the progress of our collaboration with BeiGene on the lifirafenib and mirdametinib combination," said Saqib Islam, CEO of SpringWorks. "We view vertical inhibition approaches, such as this novel combination, as a promising strategy to improve outcomes in biomarker-defined subgroups of patients that lack efficacious treatments for their cancers."

Oral Presentation at the AACR (Free AACR Whitepaper) Annual Meeting 2023:

Safety, pharmacokinetics, and antitumor activity findings from a phase 1b, open-label, dose-escalation and expansion study investigating RAF dimer inhibitor lifirafenib in combination with MEK inhibitor mirdametinib in patients with advanced or refractory solid tumors

Presenter: Benjamin Solomon, M.D., Peter MacCallum Cancer Centre, Melbourne, Australia

Session Title: Mini-symposium Session CTMS02 – Targeting the KRAS Pathway in the Clinic

Abstract #: CT033

Session Date and Time: Monday, April 17, 2023, 3:50-4:00 PM ET

This ongoing Phase 1b trial (NCT03905148) is an open-label, dose escalation and expansion study to investigate the safety, pharmacokinetics (PK) and antitumor activities of mirdametinib in combination with lifirafenib, BeiGene’s RAF dimer inhibitor, in patients with advanced or refractory solid tumors harboring RAS mutations, RAF mutations, and other MAPK pathway aberrations.

Results from the Part A dose-escalation and dose-finding study are being presented at AACR (Free AACR Whitepaper). This portion of the study was designed to evaluate the safety, tolerability, and pharmacokinetics of the combination, and determine the maximum tolerated dose and/or recommended Phase 2 dose.

As of the data cut-off of January 20, 2023, 71 patients were treated across 9 dose levels evaluating different dosing regimens. Results suggest that lifirafenib in combination with mirdametinib demonstrated a favorable safety profile, with low incidence of dose limiting toxicities and treatment-emergent adverse events that led to dose discontinuations. The most common treatment-related adverse events related to lifirafenib and/or mirdametinib (>15%) were dermatitis acneiform (42%), fatigue (32%), diarrhea (27%), platelet count decreased (18%), alopecia (18%), nausea (17%) and alanine aminotransferase increased (16%).

The combination showed antitumor activity in patients with various KRAS, NRAS, and BRAF mutations across several solid tumor types, including low-grade serous ovarian cancer (LGSOC), non-small cell lung cancer (NSCLC), and endometrial cancer. Among 62 efficacy-evaluable patients, 14 patients (23%) had confirmed objective responses. Of 17 patients with LGSOC treated, 10 patients (59%) had objective responses, with median duration of treatment of approximately 26 months. Of the 4 endometrial cancer patients treated, 2 (50%) had objective responses in tumors that harbor BRAF fusion mutation or KRAS mutation, respectively. Of the 11 patients with NSCLC treated, 2 (18%) had objective responses in tumors that harbor NRAS mutation or BRAF V600E mutation, respectively. These data support the advancement of this combination into the dose-expansion portion of the study, which will focus on a biomarker selected patient population with a tumor agnostic approach. The expansion is expected to start in the second half of 2023.

"Our findings indicate that the combination of lifirafenib and mirdametinib treatment demonstrated antitumor activity in patients with various KRAS, NRAS, and BRAF mutations across several solid tumor types known to be driven by the MAPK pathway and for which current treatment options are limited," said Benjamin Solomon, MBBS, PhD, FRACP, medical oncologist at Peter MacCallum Cancer Centre in Melbourne, Australia. "We are pleased with the risk-benefit profile seen to date with this combination and look forward to the further clinical investigation in the dose-expansion portion of the study."

About Lifirafenib

Lifirafenib (BGB-283) is an investigational novel small molecule designed to inhibit both monomeric and dimeric RAF kinase. Lifirafenib has demonstrated antitumor activity in preclinical models and in cancer patients with tumors harboring BRAF V600E mutations and non-V600E BRAF mutations, in which the monomeric form of RAF is implicated, as well as KRAS/NRAS mutations, in which the dimeric form of RAF is implicated.

About Mirdametinib

Mirdametinib is an investigational, oral, allosteric small molecule MEK inhibitor. Mirdametinib is designed to inhibit MEK1 and MEK2, which occupy pivotal positions in the MAPK pathway. The MAPK pathway is a key signaling network that regulates cell growth and survival and that plays a central role in multiple oncology and rare disease indications when genetically altered.

Mirdametinib is in development as a monotherapy treatment for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) and low-grade glioma (LGG), and as a combination therapy for the treatment of several subsets of biomarker-defined metastatic solid tumors. To date, over 300 subjects have been exposed to treatment with mirdametinib across clinical trials, with preliminary evidence of clinical activity against tumors driven by over-activated MAPK signaling.

The U.S. Food and Drug Administration (FDA) and the European Commission granted Orphan Drug designation for mirdametinib for the treatment of NF1, and the FDA granted Fast Track designation for the treatment of patients ≥ 2 years of age with NF1-PN that are progressing or causing significant morbidity.

BioLineRx Announces Publication in Nature Medicine of its GENESIS Phase 3 Clinical Trial Data Evaluating Motixafortide and G-CSF in Stem Cell Mobilization for Autologous Transplantation in Multiple Myeloma

On April 17, 2023 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a pre-commercial-stage biopharmaceutical company focused on oncology, reported the publication of data from the Company’s GENESIS Phase 3 clinical trial in the peer-reviewed journal Nature Medicine (Press release, BioLineRx, APR 17, 2023, View Source [SID1234630138]). The international GENESIS trial evaluated the safety and efficacy of the Company’s lead investigational candidate motixafortide plus granulocyte colony-stimulating factor (G-CSF) versus placebo plus G-CSF for the mobilization of hematopoietic stem cells in patients with multiple myeloma prior to autologous stem cell transplantation (ASCT).

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Multiple myeloma is the second most common hematologic malignancy and ASCT has been shown to improve survival and plays a central role in the treatment of these patients. A meaningful number of patients, however, are unable to collect a desired number of peripheral blood CD34+ hematopoietic stem and progenitor cells (HSPC) with current treatment modalities.

The primary objective of the study was to demonstrate that one dose of motixafortide with G-CSF, compared to placebo with G-CSF, allowed more patients to mobilize ≥ 6 million CD34+ cells per kilogram of bodyweight, in up to two apheresis sessions. A secondary objective of the study was to demonstrate that one dose of motixafortide with G-CSF was superior to placebo with G-CSF in its ability to mobilize ≥ 6 million CD34+ cells per kilogram of bodyweight in just one apheresis session. The clinical trial found that all primary and secondary endpoints were achieved with a statistical significance of p<0.0001.

"Despite improvements in survival that ASCT offers patients with multiple myeloma, there has not been significant innovation in stem cell mobilization treatments in over a decade," said John DiPersio, MD, PhD, Professor of Medicine and Director of the Center for Gene and Cellular Immunotherapy at Washington University School of Medicine in St. Louis, and principal investigator of the GENESIS study. "With today’s increased use of multiple drug induction therapies and transplants in increasingly older patients, there is a corresponding increased need for new treatment options. These data highlight the potential of motixafortide plus G-CSF, if approved, to enhance the treatment options for clinicians and patients with multiple myeloma undergoing ASCT."

"This first peer-reviewed publication of results from the Phase 3 GENESIS trial is an important validation of the potential of motixafortide to address critical clinical challenges and the evolving needs of today’s ASCT treatment landscape in appropriate multiple myeloma patients," said Tami Rachmilewitz, MD, Chief Medical Officer at BioLineRx. "We look forward to continuing the development of motixafortide with the aim of advancing care for patients with multiple myeloma."

Additional GENESIS clinical trial objectives included time to engraftment of neutrophils and platelets and durability of engraftment. The motixafortide-plus-G-CSF regimen resulted in rapid and durable engraftment[i] of HSPCs following transplantation, and the regimen was also shown to have a favorable safety-profile and that it was generally well-tolerated, with the most common treatment-emergent adverse events observed being transient, grade 1/2 injection site reactions.[ii]

The study included patients that are representative of the typical multiple myeloma population undergoing ASCT, with a median age of 63 years and with ~70% of patients in both arms of the trial receiving lenalidomide-containing induction therapy. Increased age, as well as increased exposure to lenalidomide-containing induction regimens, including four-drug combination regimens, have been associated with impaired HSPC mobilization.[iii]

The study authors also performed parallel comparative FACS and single-cell transcriptional profile analyses, using GENESIS data and data from trial cohorts with other mobilization regimens, to better understand the types of cells mobilized.

The FACS analysis, as described by the study authors in Nature, found that motixafortide plus G-CSF resulted in a 10.5-fold increase in primitive HSPCs collected versus placebo plus G-CSF (p<0.0001); and significantly greater numbers of early stem and progenitor cells versus both placebo plus G-CSF (p<0.0001) and plerixafor plus G-CSF (p=0.0327). Primitive HSPCs and early stem and progenitor cells may be associated with enhanced self-renewal and regeneration.[iv] "The cohort analyses were not designed to understand potential clinical outcomes; nevertheless, we believe the findings are of interest and a compelling area for further research," said Dr. DiPersio.

A New Drug Application (NDA) for motixafortide in stem cell mobilization for autologous transplantation in multiple myeloma patients is currently under review with the U.S. Food and Drug Administration (FDA), with an assigned PDUFA date of September 9, 2023.

About the GENESIS Trial

The GENESIS trial (NCT03246529) was initiated in December 2017. GENESIS was an international, randomized, double-blind, placebo-controlled, multicenter study, evaluating the safety and efficacy of motixafortide and G-CSF, compared to placebo and G-CSF, for the mobilization of hematopoietic stem-cells for autologous transplantation in multiple myeloma patients. The primary objective of the study was to demonstrate that one dose of motixafortide with G-CSF, compared to placebo with G-CSF, allowed more patients to mobilize ≥ 6 million CD34+ cells per kilogram of bodyweight, in up to two apheresis sessions. A secondary objective of the study was to demonstrate that one dose of motixafortide with G-CSF was superior to placebo with G-CSF in its ability to mobilize ≥ 6 million CD34+ cells per kilogram of bodyweight in just one apheresis session. Additional objectives included time to engraftment of neutrophils and platelets and durability of engraftment, as well as other efficacy and safety parameters.

CD34+ cells in the GENESIS trial were assessed using both central lab and local lab data, both of which achieved statistical significance (p<0.0001) across all primary and secondary endpoints. The Nature Medicine publication focused on the study’s local lab data, as it was used for all clinical decisions in the study.

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that affects some white blood cells called plasma cells, which are found in the bone marrow. When damaged, these plasma cells rapidly spread and replace normal cells in the bone marrow with tumors. According to the American Cancer Society, in 2023, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma, and nearly 13,000 people will die from the disease in the U.S. While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.

About Autologous Stem Cell Transplantation

Autologous stem cell transplantation (ASCT) is part of the standard treatment paradigm for a number of blood cancers, including multiple myeloma. In the U.S., nearly 15,000 ASCTs are performed each year with the majority in patients with multiple myeloma. The current standard of care includes the administration of 5-8 daily doses of granulocyte colony stimulating factor (G-CSF), with or without 1-4 doses of plerixafor, and the performance of 1-4 apheresis sessions. For patients unable to mobilize sufficient numbers of cells for harvesting during this primary mobilization phase, rescue therapy is carried out, consisting of 1-4 additional doses of plerixafor on top of G-CSF, and the performance of an additional number of apheresis sessions as necessary.

Anixa Biosciences and Cleveland Clinic Present Positive Data for Phase 1 Study of Breast Cancer Vaccine

On April 17, 2023 Anixa Biosciences, Inc. (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer reported that Cleveland Clinic presented the most up-to-date data from the Phase 1 Trial of its breast cancer vaccine (Press release, Anixa Biosciences, APR 17, 2023, View Source [SID1234630137]). The data presented showed that in the vaccinated women who have been tested to date, various levels of antigen-specific T cell responses were observed at all dose levels. The presentation was made by G. Thomas Budd, M.D., of Cleveland Clinic’s Taussig Cancer Institute and principal investigator of the study. This breast cancer vaccine technology was invented at Cleveland Clinic, where the trial is being conducted, and Anixa is the exclusive worldwide licensee. The trial is funded by a grant from the U.S. Department of Defense to Cleveland Clinic.

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The Phase 1a study is designed to evaluate the safety of the vaccine, identify the Maximum Tolerated Dose (MTD), and monitor the immune response in vaccinated women. All participants in the Phase 1a study are women who have had triple negative breast cancer (TNBC) within the last three years and have been curatively treated having undergone standard of care. At the time of vaccination, these participants are tumor-free, as determined by standard diagnostic techniques, but are at high risk of recurrence.

"We are testing this vaccine to determine if a vaccinated patient’s immune system is trained to destroy cancer cells expressing α-lactalbumin, a protein found on TNBC cancer cells and not on normal cells. To evaluate the vaccination effect, immune mediated biomarkers of T cell activation and antibody production specific against α-lactalbumin are measured. We are heartened by the data, and look forward to additional studies," stated Dr. Amit Kumar, Chairman and CEO of Anixa Biosciences.

"We are pleased that varying degrees of antigen-specific T cell responses were observed at all dose levels tested to date, however, the Phase 1 trial is not designed to determine whether the responses are sufficient to prevent recurrence or primary tumorogenesis, said Dr. Budd. "We expect successive studies to determine how effective the immune responses are in preventing cancer."

About Triple-Negative Breast Cancer

One in eight women in the U.S. will be diagnosed with an invasive breast cancer at some point in their lives. Approximately 10-15% of those diagnoses are TNBC, however TNBC accounts for a disproportionately higher percentage of breast cancer deaths and has a higher rate of recurrence. This form of breast cancer is twice as likely to occur in African-American women, and approximately 70% to 80% of the breast tumors that occur in women with mutations in the BRCA1 genes are triple-negative breast cancer.

Allogene Therapeutics Presents Interim Phase 1 Data on ALLO-316 in Renal Cell Carcinoma at the American Association of Cancer Research (AACR) Annual Meeting

On April 17, 2023 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer, reported interim data from its Phase 1 TRAVERSE trial of ALLO-316, the Company’s first AlloCAR TTM investigational product candidate for solid tumors, in an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Orlando, Florida (Press release, Allogene, APR 17, 2023, View Source [SID1234630136]). The presentation follows the release of initial ALLO-316 data reported at the Company’s R&D Showcase event in November 2022.

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The ongoing Phase 1 TRAVERSE study is enrolling patients with advanced or metastatic renal cell carcinoma (RCC) who have progressed on standard therapies that include an immune checkpoint inhibitor and a VEGF-targeting therapy. Emerging data from this trial have demonstrated the potential of an AlloCAR T to treat CD70 expressing RCC. In this trial, ALLO-316 showed early anti-tumor activity with deepening responses over time.

"CAR T therapy has revolutionized the treatment of several hematologic malignancies, but its application to solid tumors has been an ongoing industry challenge," said Zachary Roberts, M.D., Ph.D., Executive Vice President of Research & Development. "Early safety and efficacy data from the ongoing Phase 1 ALLO-316 dose escalation trial suggest the possibility for an off-the-shelf CAR T product to make inroads into solid tumors. Additionally, preliminary translational data confirm preclinical results showing the potential of our Dagger technology. This feature of ALLO-316 is designed to prevent premature AlloCAR T cell rejection, allowing marked cell expansion and persistence, even at low CAR T cell doses."

"I am encouraged by these data highlighting the potential of an allogeneic CAR T as a new and much needed treatment modality for patients with renal cell carcinoma," said Samer A. Srour, M.D., The University of Texas MD Anderson Cancer Center. "Initial data from the TRAVERSE trial provides a proof-of-concept for the successful application of this novel CAR T product in the treatment of advanced renal cell carcinoma."

As of the March 23, 2023 data cutoff, 19 patients were enrolled in the Phase 1 trial, 10 of whom had RCC confirmed to express CD70. The median time from enrollment to the start of therapy was five days. In the ongoing dose escalation phase of the TRAVERSE trial, patients will receive lymphodepletion followed by ALLO-316 at one of four cell dose levels (DL1= 40M cells, DL2= 80M cells, DL3=120M cells, DL4= 240M cells). The data reported to date is primarily from the DL1 and DL2 cohorts.

Anti-tumor activity was primarily observed in patients with tumors confirmed to express CD70.
Among 18 patients evaluable for efficacy, the disease control rate (DCR) was 89%. In the 10 patients whose tumors were known to express CD70, the disease control rate was 100%, which included three patients who achieved partial remission (two confirmed, one unconfirmed). The longest response lasted until month eight. There was a trend toward greater tumor shrinkage in patients with higher levels of CD70 expression.

All Patients
(n=18) CD70+ Patients
(n=10)
Overall Response Rate (ORR), n (%) 3 (17) 3 (30)
Disease Control Rate (DCR), n (%) 16 (89) 10 (100)
There were 19 patients evaluable for safety. To date, ALLO-316 has demonstrated an adverse event profile generally consistent with autologous CAR T therapies. One dose-limiting toxicity of Grade 3 autoimmune hepatitis occurred in the second dose level. Cytokine release syndrome (CRS) was all low-grade with the exception of one Grade 3. Neurotoxicity, which is now defined more broadly, was generally low grade and reversible with most events being fatigue or headache. There were no cases of immune effector cell-associated neurotoxicity syndrome (ICANS). Infections occurred in eight patients of which four were Grade 3+ including one Grade 5 respiratory failure due to Covid-19 infection deemed unrelated to study treatment. Grade 3+ prolonged cytopenia was observed in three patients (16%). There were no cases of graft-versus-host disease (GvHD).

All Patients
(n=19)
All Grades
N (%) Gr 3+
N (%)
CRS 11 (58) 1 (5)
Infusion-Related Reaction 1 (5) 0
Neurotoxicity 13 (68) 2 (11)
ICANS 0 0
GvHD 0 0
Infection 8 (42) 4 (21)
Prolonged Gr3+ Cytopenia 0 3 (16)
The Dagger technology, which is a feature of ALLO-316, is designed to resist rejection of AlloCAR T cells by the host immune cells, thereby supporting expansion and enabling a prolonged window of persistence during which AlloCAR T cells can target and destroy cancer cells. Initial translational data from the TRAVERSE trial demonstrates the suppression of host T cells and marked peak expansion of ALLO-316 despite the relatively low cell doses tested. In addition to ALLO-316, the Company plans to deploy Dagger technology to potentially enhance the persistence and activity of next generation AlloCAR T products.

About ALLO-316 (TRAVERSE)
ALLO-316, an AlloCAR T investigational product targets CD70, which is highly expressed in renal cell carcinoma (RCC). CD70 is also selectively expressed in several cancers, creating the potential for ALLO-316 to be developed across a variety of both hematologic malignancies and solid tumors. The ongoing Phase 1 TRAVERSE trial is designed to evaluate the safety, tolerability, and activity of ALLO-316 in patients with advanced or metastatic clear cell RCC. In March 2022, the U.S. Food and Drug Administration granted Fast Track Designation (FTD) based on the potential of ALLO-316 to address the unmet need for patients with difficult to treat RCC who have failed standard RCC therapies.