On November 3, 2023 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), a clinical stage immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported initial data from the monotherapy dose-escalation portion of its Phase 1/2 clinical trial for SNS-101, a conditionally active, human monoclonal antibody targeting the immune checkpoint VISTA (V-domain Ig suppressor of T cell activation) (Press release, Sensei Biotherapeutics, NOV 3, 2023, View Source [SID1234636900]). The data, to be presented in a late-breaker poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting, suggest a potential best-in-class safety and pharmacokinetic profile among VISTA blocking antibodies and the potential to overcome long-standing pharmacological challenges encountered by first generation approaches to blocking VISTA.

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"We are pleased to report favorable clinical data for SNS-101, a pioneering VISTA-blocking antibody that provides validation of our conditionally active approach. The data support that this highly innovative antibody is well tolerated across dose levels tested to date, shows linear, dose-dependent pharmacokinetics predicted preclinically to elicit immune-mediated anti-tumor activity, and a cytokine profile consistent with an absence of cytokine release syndrome," said John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics. "Data from this clinical study to date provides important initial evidence that SNS-101 can provide clinically meaningful and mechanistic differentiation from first generation anti-VISTA approaches, as indicated by SNS-101 dose levels that are at least 10 times higher than the first clinical study of a competitor VISTA antibody that was prematurely halted due to cytokine release syndrome and poor pharmacokinetics. We believe this represents a foundational clinical achievement in the pursuit of a transformational VISTA-blocking antibody, and we look forward to building on this success with additional data readouts, including efficacy analysis, expected next year."

The multi-center Phase 1/2 clinical trial is a dose escalation study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SNS-101 as both a monotherapy and in combination with Regeneron’s PD-1 inhibitor Libtayo (cemiplimab) in patients with advanced solid tumors.

Summary of reported data (as of the October 3, 2023 cutoff date):

A total of 13 patients were enrolled in the study.
In the monotherapy dose escalation arm, ten patients were enrolled across four dosing cohorts receiving SNS-101 treatment at 0.3, 1, 3, or 10 mg/kg.
In the combination arm, three patients were enrolled at the first dose level of 3.0 mg/kg of SNS-101 plus 350 mg of Libtayo (cemiplimab).
Safety, cytokine expression and pharmacokinetic data were presented for seven patients from the first three monotherapy cohorts, all of which have cleared the dose-limiting toxicity assessment period.
A total of 11 adverse events (including one serious adverse event not considered related to SNS-101) was reported in five patients, with no dose-limiting toxicities observed. Only one adverse event (Grade 2 dermatitis acneiform) was considered related to SNS-101.
There were no instances of cytokine release syndrome and no significant changes in key inflammatory cytokines over time, consistent with preclinical studies.
Pharmacokinetic data demonstrate dose-proportional exposure consistent with lack of target mediated drug disposition, no notable accumulation with repeat dosing, and linear elimination kinetics of SNS-101, in concordance with preclinical data.
"Too many patients remain underserved by existing immunotherapies. SNS-101 highlights the potential of targeting VISTA through an innovative concept, thoughtful approach and a well-executed study as Sensei has done," said Shiraj Sen, M.D., Ph.D., a medical oncologist at NEXT Oncology and investigator on the Phase 1/2 SNS-101 clinical trial. "I’m encouraged by the patient experience so far in the SNS-101 trial, including a potentially best-in-class safety profile and an every-three-week dosing schedule that helps alleviate the logistical burden imposed on patients by agents requiring more frequent administration due to their unfavorable PK profiles."

Sensei expects to report initial safety and pharmacokinetic combination data in Q1 2024, with topline monotherapy data in Q2 2024, and topline combination data in 2024.

Presentation at SITC (Free SITC Whitepaper):

Title: A phase 1/2 study of safety, tolerability and pharmacokinetics of SNS-101, a pH-sensitive anti-VISTA mAb, as monotherapy and in combination with cemiplimab in patients with advanced solid tumors
Presentation type: Poster (late breaking abstract)
Abstract Number: 1532
Date and time: Saturday, November 4, 2023, at 9 a.m. PT – 8:30 p.m. PT
Location: Exhibit Halls A and B1 – San Diego Convention Center
Lead authors: Shiraj Sen, M.D., Ph.D. and F. Donelson Smith, Ph.D.

A copy of the presentation materials will be added to the "Events & Presentations" section of the Company’s Investor Relations website at www.senseibio.com.

On November 3, 2023 Seagen Inc. (NASDAQ: SGEN) reported the first presentation of data evaluating ADCETRIS (brentuximab vedotin) in combination with an anti-PD-1 checkpoint inhibitor in non-small cell lung cancer (NSCLC) and melanoma, and shared preclinical data for an investigational CD30-directed antibody-drug conjugate (ADC) that uses a novel tripeptide linker (Press release, Seagen, NOV 3, 2023, View Source [SID1234636899]). The studies were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting, taking place November 3-5, 2023, in San Diego.

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"The combination of ADCETRIS and a PD-1 inhibitor to treat solid tumors are intriguing and support continued research," said Roger Dansey, M.D., President, Research and Development and Chief Medical Officer at Seagen. "We are also encouraged by pre-clinical results for SGN-35T, an investigational next-generation CD30-targeted ADC, and plan to begin enrolling patients in a phase 1 clinical trial soon."

Phase 2 Study of ADCETRIS plus Pembrolizumab in Solid Tumors

The Phase 2 trial SGN35-033 explored the combination of ADCETRIS with pembrolizumab in 55 patients with non-small cell lung cancer (NSCLC) and 58 patients with melanoma who either had no response to previous anti-PD-1 treatment or who experienced cancer progression after initial response to anti-PD-1 therapy (primary resistant or secondary refractory disease, respectively). NSCLC cohorts were evaluated using RECIST v1.1 and melanoma cohorts were evaluated using immune RECIST (iRECIST).

In NSCLC, the ADCETRIS and pembrolizumab combination demonstrated an objective response rate (ORR) of 8% (95% CI: 0.2, 38.5) and 14% (95% CI: 5.3, 27.9) in patients with primary (n=12) and secondary (n=43) refractory NSCLC, respectively. Disease control rates (DCR) — inclusive of complete responses, partial responses and stable disease — were 67% (CI: 34.9, 90.1) and 72% (CI: 56.3, 84.7), respectively.

In melanoma, the ADCETRIS and pembrolizumab combination demonstrated an ORR of 18% (95% CI: 3.8, 43.4) and 22% (95% CI: 10.6, 37.6), in primary (n=17) and secondary (n=41) refractory metastatic cutaneous melanoma, respectively. DCRs were 71% (CI: 44.0, 89.7) and 80% (CI: 65.1, 91.2), respectively. The study design included melanoma patients who were treated in the study within 90 days of receiving prior anti-PD-1 therapy.

The safety profile of ADCETRIS was consistent with previous studies, and no new safety signals were observed.

Increased CD8 T cell infiltration was observed in the tumor microenvironment of patients who responded to the combination treatment, suggesting potential re-sensitization to PD-1 inhibitors.

The study is currently enrolling patients in previously untreated NSCLC and head and neck cancer.

SGN-35T, a Novel ADC

SGN-35T is a next generation CD30-directed ADC that uses a novel tripeptide linker designed to preferentially release its cytotoxic payload in tumor cells to limit off-target toxicity. Preclinical data suggest that SGN-35T may be highly effective, like ADCETRIS, with the potential for improved tolerability. SGN-35T is an investigational agent, and its safety and efficacy have not been established.

In this in vitro study, SGN-35T was cytotoxic to CD30-expressing tumor cells and CD30-expressing regulatory T cells, whereas CD8-expressing T cells were unaffected by SGN-35T. The observations support future clinical investigation of SGN-35T in solid tumors.

Key Seagen Data to be Presented

Abstract Title

Abstract #

Presentation

Lead Author

Phase 2 trial of brentuximab vedotin (BV) with pembrolizumab (pembro) in patients with metastatic non-small cell lung cancer or metastatic cutaneous melanoma after progression on anti-PD-1 therapy

699

Poster

Nov. 3, 9:00 a.m. – 7:00 p.m. PT

Lee

innovaTV 207 Parts E and F: A phase 2 study of tisotumab vedotin in patients with squamous cell carcinoma of the head and neck (trial in progress)

681

Poster

Nov. 3, 9:00 a.m. – 7:00 p.m. PT

Seiwert

Activated regulatory T cells in solid tumors express CD30, which are selectively targeted by the novel anti-CD30 antibody-drug conjugate SGN-35T

1155

Poster

Nov. 3, 9:00 a.m. – 7:00 p.m. PT

O’Connor

About ADCETRIS

ADCETRIS is an ADC comprised of a CD30-directed monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seagen’s proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.

ADCETRIS is approved in seven indications in the U.S.:

Adult patients with previously untreated Stage III/IV cHL in combination with doxorubicin, vinblastine, and dacarbazine (2018)
Pediatric patients 2 years and older with previously untreated high risk cHL in combination with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (2022)
Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation (2015)
Adult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates (2011)
Adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone (2018)
Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. (2011)
Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) after prior systemic therapy (2017)
ADCETRIS has marketing authorization in more than 70 countries for relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma.

Seagen and Takeda jointly develop ADCETRIS. Under the terms of the collaboration agreement, Seagen has U.S. and Canadian commercialization rights, and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seagen and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

ADCETRIS (brentuximab vedotin) for injection U.S. Important Safety Information

BOXED WARNING

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.

CONTRAINDICATION

Contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

WARNINGS AND PRECAUTIONS

Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay, change in dose, or discontinuation of ADCETRIS.

Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.

Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.

Administer G-CSF primary prophylaxis beginning with Cycle 1 for adult patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL, and pediatric patients who receive ADCETRIS in combination with chemotherapy for previously untreated high risk cHL.

Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.

Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for infections.

Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden may be at increased risk. Monitor closely and take appropriate measures.

Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment. Avoid use in patients with severe renal impairment.

Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment. Avoid use in patients with moderate or severe hepatic impairment.

Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.

PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.

Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.

Serious dermatologic reactions: Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.

Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with preexisting GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately.

Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of preexisting diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated.

Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of this potential risk, and to use effective contraception during ADCETRIS treatment and for 2 months after the last dose of ADCETRIS. Advise male patients with female partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 4 months after the last dose of ADCETRIS.

ADVERSE REACTIONS

The most common adverse reactions (≥20% in any study) are peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, mucositis, thrombocytopenia, and febrile neutropenia.

DRUG INTERACTIONS

Concomitant use of strong CYP3A4 inhibitors has the potential to affect the exposure to monomethyl auristatin E (MMAE). Closely monitor adverse reactions.

USE IN SPECIAL POPULATIONS

Lactation: Breastfeeding is not recommended during ADCETRIS treatment.

Please see the full Prescribing Information, including BOXED WARNING, for ADCETRIS here .

On November 3, 2023 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that new and updated data from its hematology pipeline will be shared in 19 abstracts at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting from December 9 to 12 in San Diego, CA (Press release, Regeneron, NOV 3, 2023, View Source [SID1234636898]). These include research across six investigational medicines that span eight difficult-to-treat blood cancers and disorders. Together, these presentations showcase the diversity of approaches Regeneron is advancing through its hematology pipeline and its dedication to leading-edge research.

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"We are fusing our legacy of innovation with our deep scientific expertise in hematology to advance research across multiple modalities as we aim to ultimately make a meaningful impact in patients’ lives. Our data at ASH (Free ASH Whitepaper) are a testament to our progress towards this ambition," said L. Andres Sirulnik, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Hematology at Regeneron. "In addition to new results from our pivotal trials evaluating odronextamab and linvoseltamab, we are presenting findings on our growing blood disorders pipeline. Further, our presentations span emerging measures of disease that contribute to a deeper understanding of these advanced conditions, which in the future could form the basis of response-directed treatment paradigms."

At ASH (Free ASH Whitepaper), 10 abstracts will feature updated data and analyses for Regeneron’s most advanced investigational blood cancer medicine, odronextamab (CD20xCD3 bispecific antibody), in relapsed/refractory (R/R) follicular lymphoma (FL) and R/R diffuse large B-cell lymphoma (DLBCL). Among them are three oral presentations from its pivotal trial (ELM-2), including: the final analysis in R/R DLBCL patients; a comprehensive analysis of minimal residual disease status and circulating tumor DNA profiling in R/R FL and DLBCL patients; and updated analyses and long-term follow-up of efficacy, safety and patient reported outcomes in R/R FL. Furthermore, the company will share long-term survival outcomes and a responder analysis for odronextamab from a Phase 1 trial (ELM-1) in R/R DLBCL patients who have progressed after CAR-T therapy, a patient population who have a particularly dismal prognosis and limited effective treatment options. Odronextamab is currently under regulatory review for the treatment of R/R FL and R/R DLBCL by the U.S. Food and Drug Administration, with a target action date of March 31, 2024, as well as by the European Medicines Agency.

Five presentations will highlight data supporting linvoseltamab (BCMAxCD3 bispecific antibody), including the first presentation of primary endpoint results with longer follow-up from the pivotal Phase 2 trial (LINKER-MM1) in heavily pre-treated patients with multiple myeloma. Additionally, two presentations will review the latest results from three Phase 2 studies evaluating pozelimab (C5 antibody) in combination with Alnylam Pharmaceuticals, Inc.’s cemdisiran (siRNA C5 inhibitor) in patients with paroxysmal nocturnal hemoglobinuria, a rare blood disorder.

Regeneron presentations at ASH (Free ASH Whitepaper):

Abstract title Abstract Presenting/Lead Author Presentation
date/time
(PT)
Odronextamab
Circulating Tumor DNA Analysis Associates with Progression-Free Survival (PFS) with Odronextamab Monotherapy in Relapsed/Refractory (R/R) Follicular Lymphoma (FL) and Diffuse Large B-Cell Lymphoma (DLBCL): Identification of Minimal Residual Disease Status and High-Risk Subgroups from the Phase 2 ELM-2 Study
#427

Oral Presentation Jon E. Arnason Sunday,
December 10,
9:30 AM

Final Analysis of the Phase 2 ELM-2 Study: Odronextamab in Patients with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
#436

Oral Presentation Sabarish Ram Ayyappan Sunday,
December 10,
10:15 AM

Maintenance of Moderate to High Levels of Functioning and Quality of Life with Odronextamab Monotherapy in Patients with Relapsed or Refractory Follicular Lymphoma
#669

Oral Presentation Benoît Tessoulin Sunday,
December 10,
5:00 PM

Odronextamab Monotherapy for the Treatment of Relapsed/Refractory (R/R) Follicular Lymphoma (FL) and Diffuse Large B-Cell Lymphoma (DLBCL): Focus on Clinical Pharmacology and Pharmacometrics in the ELM-1 and ELM-2 Studies
#1436

Poster Presentation Min Zhu Saturday,
December 9,
5:30-7:30 PM

Results of a Second, Prespecified Analysis of the Phase 2 Study ELM-2 Confirm High Rates of Durable Complete Response with Odronextamab in Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) with Extended Follow-Up
#3041

Poster Presentation Jose (J.C.) C. Villasboas Bisneto Sunday,
December 10,
6:00-8:00 PM

Trial in Progress: Phase 1 Trial Evaluating the Safety and Tolerability of Odronextamab in Combination with Cemiplimab in Relapsed/Refractory Aggressive B-cell Non-Hodgkin Lymphoma
#3100

Poster Presentation
Cecilia Carpio Sunday,
December 10,
6:00-8:00 PM

Odronextamab Demonstrates Durable Complete Responses in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Progressing After CAR-T Therapy: Outcomes from the ELM-1 Study
#4461

Poster Presentation Jennifer L. Crombie Monday,
December 11,
6:00-8:00 PM

Health-Related Quality of Life and Symptoms in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma Treated with Odronextamab Monotherapy in the Phase 2 ELM-2 Study
#4504

Poster Presentation Elżbieta Iskierka-Jażdżewska Monday,
December 11,
6:00-8:00 PM

Key prognostic factors in patients with relapsed/refractory follicular lymphoma: An evidence based systematic literature and medical review
#7261

Online publication Ana Jimenéz-Ubieto N/A

Key prognostic factors in patients with relapsed/refractory diffuse large B-cell lymphoma: An evidence based systematic literature and medical review
#7258

Online Publication Bastien von Tresckow N/A

Linvoseltamab
Incidence of Second Primary Malignancies in Medicare-Insured Patients in the US with Triple-Class Exposed Relapsed/Refractory Multiple Myeloma
#912

Oral Presentation Sikander Ailawadhi Monday,
December 11,
4:00 PM

Health-Related Quality of Life (HRQoL) Among Patients with Triple-Class Exposed Relapsed/Refractory Multiple Myeloma (RRMM) Treated with Linvoseltamab in LINKER-MM1: Interim Assessment Up to 36 Weeks of Treatment
#3359

Poster Presentation James E. Hoffman Sunday,
December 10,
6:00-8:00 PM

Trial In Progress: A Phase 2 Study of Linvoseltamab for the Treatment of High-Risk Smoldering Multiple Myeloma (LINKER-SMM1)
#3393

Poster Presentation Paula Rodriguez-Otero Sunday,
December 10,
6:00-8:00 PM

Real-World Study of Patients with Triple-Class Exposed Relapsed/Refractory Multiple Myeloma: Analysis Across a Spectrum of Advanced Disease Stage Medicare Patients in the United States
#3773

Poster Presentation Qiufei Ma Sunday,
December 10,
6:00-8:00 PM

Patterns of Response to 200 mg Linvoseltamab in Patients with Relapsed/Refractory Multiple Myeloma: Longer Follow-up of the LINKER-MM1 study
#4746

Poster Presentation Sundar Jagannath Monday,
December 11,
6:00-8:00 PM

Pozelimab + Cemdisiran*
Psychometric Evaluation of the PNH Symptom Questionnaire (PNH-SQ) Among Patients With Paroxysmal Nocturnal Hemoglobinuria from Three Phase 2 Clinical Trials With Pozelimab Monotherapy or in Combination With Cemdisiran
#3752

Poster Presentation Christopher Hartford Sunday,
December 10,
6:00-8:00 PM

52-Week Open-Label Extension Data from A Phase 2 Study Evaluating the Safety and Efficacy of Pozelimab and Cemdisiran Combination Therapy in Patients with Paroxysmal Nocturnal Hemoglobinuria Who Switched from Eculizumab
#2716

Poster Presentation Richard J. Kelly Sunday,
December 10,
6:00-8:00 PM

REGN7999 (TMPRSS6 inhibitor)
Single Ascending Doses of REGN7999, A Monoclonal Antibody Inhibitor of TMPRSS6, Increase Serum Hepcidin And Cause Deep, Sustained Reductions in Serum Iron in Healthy Human Volunteers
#3841

Poster Presentation Nikhil Singh Monday,
December 11,
6:00-8:00 PM

REGN7257 (IL2RG antibody)
Blockade of Common Gamma Chain Cytokine Signaling with REGN7257, an Interleukin 2 Receptor Gamma (IL2RG) Monoclonal Antibody, in Combination with Costimulatory Blockers Delayed Skin Graft Rejection in Mice
#2550

Poster Presentation Audrey Le Floc’h Sunday,
December 10,
6:00-8:00 PM

REGV131-LNP1265 (in vivo CRISPR/Cas9-based Factor 9 gene insertion therapy)**
Novel Approaches for Gene-Based Therapies: Targeted Gene Insertion of Factor 9 as a Durable Treatment for Hemophilia B
Invited Talk Leah Sabin Saturday,
December 9,
9:30-10:45 AM


*In collaboration with Alnylam Pharmaceuticals, Inc.
**In collaboration with Intellia Therapeutics, Inc.

The potential uses of odronextamab, linvoseltamab, pozelimab, cemdisiran, REGN7999, REGN7257, and REGV131-LNP1265 described above are investigational, and their safety and efficacy have not been fully evaluated by any regulatory authority.

About Regeneron in Hematology
At Regeneron, we’re applying more than three decades of biology expertise with our proprietary VelociSuite technologies to develop medicines for patients with diverse blood cancers and rare blood disorders.

Our blood cancer research is focused on bispecific antibodies that are being investigated both as monotherapies and in combination with each other and emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop customized and potentially synergistic cancer treatments.

Our research and collaborations to develop potential treatments for rare blood disorders include explorations in antibody medicine, gene editing and gene-knockout technologies, and investigational RNA-approaches focused on depleting abnormal proteins or blocking disease-causing cellular signaling.

If you are interested in learning more about our clinical trials, please contact us ([email protected] or 844-734-6643) or visit our clinical trials website.

On November 3, 2023 RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based therapeutics company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in inflammatory diseases and oncology, reported safety and efficacy data from its Phase 2 trial of FLX475 (tivumecirnon) in patients with advanced non-small cell lung cancer (NSCLC) who had no prior checkpoint inhibitor therapy (Press release, RAPT Therapeutics, NOV 3, 2023, https://investors.rapt.com/news-releases/news-release-details/rapt-therapeutics-announces-positive-data-including-objective [SID1234636896]). The trial evaluated FLX475, an oral small molecule CCR4 antagonist designed to block the migration of regulatory T cells, in combination with the checkpoint inhibitor pembrolizumab. In this cohort of NSCLC patients, 36 patients were evaluable for efficacy, of which 20 were PD-L1 positive. In these PD-L1 positive patients, the combination of FLX475 and pembrolizumab showed a 40% (8/20) confirmed ORR and a median PFS of 6.3 months as of the data cut off date, with seven patients continuing on study. For comparison, historical pembrolizumab monotherapy activity in checkpoint inhibitor-naïve and previously-treated NSCLC patients showed a confirmed ORR of 18% and a median PFS of 4.0 months. The confirmed ORR for the combination of FLX475 and pembrolizumab in PD-L1 low and high subsets were 38% (6/16) and 50% (2/4), respectively. For comparison, the ORR for pembrolizumab monotherapy in the PD-L1 low and high subsets has been previously reported as 10% and 30%, respectively.

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The data were presented today in a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting being held in San Diego. The presenting author was Julie Brahmer, M.D., Co-director of the Upper Aerodigestive Department and Professor of Oncology, Johns Hopkins University.

"We are excited by the response rates and PFS data for FLX475 in combination with a checkpoint inhibitor in this cohort of NSCLC patients. The data from this cohort, which will continue to mature and potentially improve, met our criteria to advance development of FLX475," said Brian Wong, M.D., Ph.D., President and Chief Executive Officer of RAPT. "We are particularly intrigued to see differentiating efficacy in patients with cool (PD-L1 low) tumors, which are typically poorly responsive to checkpoint inhibitors and checkpoint inhibitor combinations, such as those with anti-TIGIT antibodies. Along with RPT193, we now have two internally discovered compounds that have demonstrated clinical proof of concept in large, commercially attractive indications."

Phase 2 Data Summary in CPI-naïve NSCLC Patients (n=20)

PD-L1 Status Confirmed Responses (n) Confirmed ORR
Positive (TPS ≥1%) 8/20 40%
Low (TPS 1-49%) 6/16 38%
High (TPS ≥50%) 2/4 50%
At the time of data cut off, there was one additional response among the PD-L1 low patients awaiting confirmation.

The combination of FLX475 and pembrolizumab was well tolerated in this Phase 2 NSCLC cohort. The most common treatment-emergent adverse event deemed related to study treatment was QT prolongation that was asymptomatic and reversible. FLX475 has now been dosed in more than 300 patients with various advanced cancers and has been generally well tolerated, and the combination with pembrolizumab has not increased immune-related toxicity beyond that expected with pembrolizumab alone.

In previous disclosures, FLX475 showed durable objective responses as monotherapy in an EBV+ lymphoma, as well as in combination with pembrolizumab in EBV+ gastric cancer.

Webcast Conference Call Information
RAPT will host a webcast conference call today, November 3, 2023 at 10:00 a.m. PT. To join the conference call via phone and participate in the live Q&A session, please pre-register online here to receive a telephone number and unique passcode required to enter the call. The live webcast and audio archive of the presentation may be accessed on the RAPT Therapeutics website at https://investors.rapt.com/events-and-presentations.

About FLX475
FLX475 (tivumecirnon) is a small molecule CCR4 antagonist designed to block the migration of regulatory T cells (Treg) specifically into tumors, but not healthy tissues. Treg represent a dominant pathway for downregulating the immune response, generally correlate with poor clinical outcomes, and may limit the effectiveness of currently available therapies such as checkpoint inhibitors. FLX475 may restore naturally occurring antitumor immunity alone and may synergize with a variety of both conventional and immune-based therapies, such as radiation, chemotherapy, checkpoint inhibitors, immune stimulators, cancer vaccines, and adoptive T cell therapy.

On November 3, 2023 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported financial results for the third quarter ended September 30, 2023 and provided a business update (Press release, Protara Therapeutics, NOV 3, 2023, View Source [SID1234636895]).

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"Progress continues across our TARA-002 clinical development programs, with patient dosing now underway in the ADVANCED-2 trial in patients with non-muscle invasive bladder cancer (NMIBC) and the STARBORN-1 trial in pediatric patients with lymphatic malformations (LMs)," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "We remain keenly focused on execution across all our ongoing clinical studies and remain on track to report preliminary results from the expansion portion of the ADVANCED-1 trial of TARA-002 in patients with NMIBC in the first half of 2024. With a cash runway into the second quarter of 2025, we believe we are well positioned to achieve key milestones in our TARA-002 development programs."

Recent Highlights

TARA-002 in NMIBC

In September 2023, the Company announced dosing of the first patient in ADVANCED-2, a Phase 2 open-label trial evaluating intravesical TARA-002 in up to 102 NMIBC patients with carcinoma in situ (CIS) (± Ta/T1) who are Bacillus Calmette-Guérin (BCG)-naïve (n=27) and BCG-unresponsive (n=75). Trial subjects will receive an induction with or without a reinduction course of six weekly intravesical instillations of TARA-002, followed by a maintenance course of three weekly installations every three months in the BCG-unresponsive cohort.

As previously announced, patient dosing is underway in the Phase 1b ADVANCED-1EXP study, an open-label expansion trial evaluating intravesical TARA-002 at the 40KE1 dose in up to 12 CIS patients, including BCG-naïve, BCG-unresponsive, and BCG-inadequately treated patients. The Company remains on track to report preliminary results in the first half of 2024. The primary endpoint of the trial is the complete response rate at three months.
TARA-002 in LMs

In October 2023, the Company announced dosing of the first patient in STARBORN-1, a Phase 2 clinical trial of TARA-002 in pediatric patients with macrocystic and mixed-cystic LMs. Including an age de-escalation safety lead-in, the trial will enroll approximately 30 patients who will receive up to four injections of TARA-002 spaced approximately six weeks apart. The primary endpoint of the trial is the proportion of participants with macrocystic and mixed cystic LMs who demonstrate clinical success, defined as having either a complete response (90% to 100% reduction from baseline in total LM volume) or substantial response (60% to less than 90% reduction in total LM volume) as measured by axial imaging.
IV Choline Chloride Program

The Company continues to engage with the U.S. Food and Drug Administration and plans to use both regulatory feedback and results from its prevalence study to inform next steps for the IV Choline Chloride development program.
Third Quarter 2023 Financial Results

As of September 30, 2023, cash, cash equivalents and investments were $74.0 million. The Company expects its current cash, cash equivalents and investments will be sufficient to fund its planned operations into the second quarter of 2025.
Research and development expenses for the third quarter of 2023 increased to $6.2 million from $3.5 million during the third quarter of 2022, primarily reflecting an increase in expenses related to non-clinical and clinical trial activities for TARA-002 of $2.2 million as well as $0.4 million of increased employee expenses inclusive of stock-based compensation.
General and administrative expenses for both the third quarter of 2023 and 2022 were $4.5 million.
For the third quarter of 2023, Protara reported a net loss of $9.9 million, or $0.87 per share, compared with a net loss of $7.7 million, or $0.68 per share, for the same period in 2022. Net loss for the third quarter of 2023 included approximately $1.4 million of stock-based compensation expenses.
About Non-Muscle Invasive Bladder Cancer

Bladder cancer is the 6th most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle.

About Lymphatic Malformations

Lymphatic malformations (LMs) are rare, congenital malformations of lymphatic vessels resulting in the failure of these structures to connect or drain into the venous system. Most LMs are present in the head and neck region and are diagnosed in early childhood during the period of active lymphatic growth, with more than 50% detected at birth and 90% diagnosed before the age of three years. The most common morbidities and serious manifestations of the disease include compression of the upper aerodigestive tract, including airway obstruction requiring intubation and possible tracheostomy dependence; intralesional bleeding; impingement on critical structures, including nerves, vessels, lymphatics; recurrent infection, and cosmetic and other functional disabilities.

About IV Choline Chloride

IV Choline Chloride is an investigational, intravenous (IV) phospholipid substrate replacement therapy initially in development for patients receiving parenteral nutrition (PN). Choline is a known important substrate for phospholipids that are critical for healthy liver function. Because PN patients cannot sufficiently absorb adequate levels of choline and no available PN formulations contain sufficient amounts of choline to correct this deficiency, PN patients often experience a prolonged progression to hepatic failure and death, with the only known intervention being a dual small bowel/liver transplant. IV Choline Chloride has been granted Orphan Drug Designation by the FDA for the prevention of choline deficiency in PN patients.

About TARA-002 in LMs

TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and of LMs, for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil in Japan and approved in Taiwan by Chugai Pharmaceutical Co., Ltd. Protara has successfully shown manufacturing comparability between TARA-002 and OK-432.

When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a strong immune cascade. Neutrophils, monocytes, and lymphocytes infiltrate the abnormal cells and various cytokines, including interleukins IL-2, IL-6, IL-8, IL-10, IL-12, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha are secreted by immune cells to induce a strong inflammatory reaction and destroy the abnormal cells.