On November 2, 2023 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that updated data from multiple trials across its clinical program for revumenib, the Company’s highly selective, oral menin inhibitor, will be featured in three poster presentations at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held December 9-12, 2023, in San Diego, California (Press release, Syndax, NOV 2, 2023, View Source [SID1234636797]). Copies of the abstracts are now available online via the ASH (Free ASH Whitepaper) website at www.hematology.org.

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 look forward to sharing updated data, which we believe continue to underscore revumenib’s potential to serve as a first- and best-in-class treatment option for patients with KMT2Ar and mNPM1 acute leukemia across a variety of settings as monotherapy and in combination with standard of care agents," said Michael A. Metzger, Chief Executive Officer. "Following recently reported positive topline data from our pivotal AUGMENT-101 trial, and with an NDA filing on track for year-end, we are excited to finish what has thus far been a transformational year with several key data updates at ASH (Free ASH Whitepaper)."

Phase 1/2 AUGMENT-101 Trial

Pivotal Phase 2 Portion

The Company previously announced positive topline data from the protocol-defined pooled analysis of the pivotal Phase 2 portion of the AUGMENT-101 trial. The trial met its primary endpoint with a complete remission (CR) or a CR with partial hematological recovery (CRh) rate of 23% at the interim analysis of the pooled KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) cohorts (p-value = 0.0036). Based on the Independent Data Monitoring Committee (IDMC) recommendation, the Company stopped the trial to further accrual in the KMT2Ar cohorts. Syndax continues to expect to submit a New Drug Application (NDA) for revumenib for the treatment of relapsed/refractory (R/R) KMT2Ar acute leukemia to the U.S. Food and Drug Administration by year-end under the Real-Time Oncology Review (RTOR) program. Full data from the pivotal portion of the study will be reported at the meeting.

Abstract Number: 2907
Title: Revumenib Monotherapy in Patients with Relapsed/Refractory KMT2Ar Acute Leukemias: Efficacy and Safety Results from the Augment-101 Phase 1/2 Study
Presenter: Ibrahim Aldoss, M.D.
Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Session Date: Sunday, December 10, 2023
Presentation Time: 6:00 – 8:00 p.m. PT

Phase 1/2 SAVE Study

The Phase 1/2 SAVE study is an investigator-sponsored trial of the all-oral regimen of revumenib, venetoclax, and ASTX727 (fixed-dose combination of decitabine and cedazuridine) in children and adults with R/R AML and mixed phenotype acute leukemias. As of a data cutoff date of July 20, 2023, eight patients were enrolled, with 2.5 median prior lines of therapy.

Seven of eight patients were response-evaluable, and all seven attained a morphologic remission (overall response rate of 100%). Three patients transitioned to hematopoietic stem-cell transplantation (HSCT) following response. Two patients are in continued remission and have started maintenance treatment with revumenib. Enrollment in the study is ongoing, and updated data will be presented at the meeting.

The combination was well tolerated in this relapsed and refractory population. Grade ≥3 treatment related adverse events (TRAEs) were febrile neutropenia (63%), decreased platelets count (25%), and decreased neutrophil count (25%). There was one dose-limiting toxicity (DLT), Grade 4 prolonged thrombocytopenia and neutropenia. There were no deaths due to TRAEs and no Grade 3 or higher QTc prolongation occurred.

Abstract Number: 58
Title: Early Results of the Phase I/II Study Investigating the All-Oral Combination of the Menin Inhibitor Revumenib (SNDX-5613) with Decitabine/Cedazuridine (ASTX727) and Venetoclax in Acute Myeloid Leukemia (SAVE)
Presenter: Ghayas Issa, M.D.
Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Upcoming Therapies in Newly Diagnosed and Relapsed/Refractory AML
Session Date: Saturday, December 9, 2023
Session Time: 9:30 – 11:00 a.m. PT
Presentation Time: 10:15 a.m. PT

Revumenib Maintenance Therapy Post-HSCT

The ASH (Free ASH Whitepaper) abstract #4950 describes data from AUGMENT-101 Phase 1 patients who received revumenib maintenance therapy, including some ongoing for more than one year after HSCT. Revumenib duration of treatment in the maintenance setting at the time of this analysis ranged from 23 to 588 days, with treatment ongoing for five of the nine patients. CRc (CR + CRh + CRp + CRi + MLFS) was maintained in six of nine patients after HSCT and maintenance revumenib. One patient with reported minimal residual disease (MRD) after HSCT converted to MRD negative status following initiation of revumenib maintenance therapy. MRD negative remissions were maintained in five patients as of the data cutoff. Three patients remain on revumenib maintenance therapy for more than one-year post-transplant. The presentation will include longer follow-up of these patients and data from the patients in the pivotal portion of the AUGMENT-101 trial.

Abstract Number: 4950
Title: Revumenib Maintenance Therapy Following Revumenib-Induced Remission and Transplant
Presenter: Andrius Žučenka, M.D.
Session Name: 723. Allogeneic Transplantation: Long-term Follow-up and Disease Recurrence: Poster III
Session Date: Monday, December 11, 2023
Presentation Time: 6:00 – 8:00 p.m. PT

About Revumenib

Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged, also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and NPM1-mutant AML. Revumenib was granted Orphan Drug Designation by the FDA and European Commission for the treatment of patients with AML, and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted BTD by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement. Syndax expects to complete an NDA submission for KMT2Ar acute leukemia under the Oncology Center of Excellence Review RTOR Program by year-end 2023.

About the AUGMENT-101 trial

AUGMENT-101 is a Phase 1/2 open-label trial designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of orally administered revumenib. The Phase 1 dose escalation portion of AUGMENT-101 included two cohorts based on concomitant treatment with a strong CYP3A4 inhibitor. Arm A enrolled patients not receiving a strong CYP3A4 inhibitor, while Arm B enrolled patients receiving a strong CYP3A4 inhibitor. The Phase 2 pivotal portion of AUGMENT-101 has enrolled R/R patients across the following trial populations: patients with mNPM1 AML, patients with KMT2Ar AML, and patients with KMT2Ar ALL. Following the receipt of Breakthrough Therapy designation from the FDA for revumenib for the treatment of R/R acute leukemia harboring a KMT2A rearrangement, regardless of age or tumor type, and based on discussions with the FDA, the Company decided to pool data from the AUGMENT-101 cohorts enrolling R/R KMT2Ar AML and R/R KMT2Ar ALL. Based on the Independent Data Monitoring Committee (IDMC) recommendation at the protocol pre-specified interim analysis, the Company stopped the trial to further accrual in the KMT2A cohorts. The trial continues to enroll R/R patients with mNPM1 AML and expects to complete enrollment of this cohort by year-end. The primary endpoint for each of the cohorts is efficacy as measured by complete remission rate (CR + CRh) per protocol, with secondary endpoints including duration of response (DOR) and overall survival (OS).

About KMT2A (MLL) Rearranged Acute Leukemia

Rearrangements of the KMT2A (mixed lineage leukemia or MLL) gene give rise to KMT2Ar acute leukemia that is known to have a poor prognosis, with less than 25% of adult patients surviving past five years. KMT2A genes produce fusion proteins that require interaction with the protein called menin to drive leukemic cancer growth. Disruption of the menin-KMT2Ar interaction has been shown to halt the growth of KMT2Ar leukemic cells.

KMT2Ar acute leukemia can phenotypically appear as AML, ALL, or mixed phenotype acute leukemia (MPAL) and is routinely diagnosed through currently available cytogenetic or molecular diagnostic techniques. The median overall survival (OS) after standard of care first-line treatment, including intensive chemotherapy and transplant, is less than one year and the majority of patients suffer relapse within five years. Most R/R patients treated with second-line therapy relapse within the first year. With third line treatment or beyond, only a small percentage of patients achieve complete remission (CR), and the median OS is less than three months. There are currently no approved therapies indicated for KMT2A-rearranged acute leukemia.

About NPM1-Mutant Acute Myeloid Leukemia

NPM1-mutant AML, which is distinguished by mutations in the NPM1 gene that drive the leukemic phenotype, is the most common type of cytogenetically normal adult AML and represents approximately 30% of all adult AML cases. This subtype of AML has a five-year overall survival rate of approximately 50%. Similar to KMT2A-rearranged acute leukemia, NPM1-mutant AML is highly dependent on the expression of specific developmental genes shown to be negatively impacted by inhibitors of the menin-KMT2A interaction. NPM1-mutant AML is routinely diagnosed through currently available screening techniques. There are currently no approved therapies indicated for NPM1-mutant AML.

On November 2, 2023 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that results from the pivotal AGAVE-201 trial of axatilimab, an anti-CSF-1R antibody, in adult and pediatric patients with chronic graft-versus-host disease (cGVHD), will be featured during the Plenary Scientific Session at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held December 9-12, 2023, in San Diego, California (Press release, Syndax, NOV 2, 2023, View Source [SID1234636796]).

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!

"Inclusion of AGAVE-201 in this year’s ASH (Free ASH Whitepaper) plenary session further supports our belief that axatilimab has the potential to serve as a highly differentiated therapeutic option for patients with chronic GVHD," said Michael A. Metzger, Chief Executive Officer. "We believe axatilimab’s best-in-category profile and unique mechanism of action positions it as an important addition to the chronic GVHD treatment armamentarium, if approved. We look forward to sharing the full dataset next month."

The Company and its partner, Incyte, previously announced positive topline data from the pivotal AGAVE-201 trial of axatilimab in patients with cGVHD following two or more prior lines of therapy. All three dose cohorts, 0.3 mg/kg every two weeks, 1.0 mg/kg every two weeks, and 3.0 mg/kg every four weeks, met the primary endpoint. The overall response rate within the first six months of treatment at the 0.3 mg/kg dose was 74%, and 60% of these patients were still responding at one year. Furthermore, axatilimab was generally well tolerated, and the most common adverse events were consistent with on-target effects and prior trials. Syndax and Incyte expect to submit a BLA filing by year-end 2023.

Abstract Number: 1
Title: Safety and Efficacy of Axatilimab at 3 Different Doses in Patients with Chronic Graft-Versus-Host Disease (AGAVE-201)
Presenter: Daniel Wolff, M.D.
Session Name: Plenary Scientific Session
Session Date: Sunday, December 10, 2023
Session Time: 2:00 – 4:00 PM PT
Presentation Time: 2:00 PM PT

Axatilimab Preclinical Data

In addition, preclinical data detailing the anti-inflammatory and anti-fibrotic mechanism through which axatilimab is thought to impact the disease process in cGVHD will be featured during a poster session.

Details for the presentation are as follows:

Abstract Number: 2540
Title: Axatilimab Ameliorates Inflammation and Fibrosis by Targeting the Macrophages in a Preclinical Model of Chronic GVHD
Presenter: Anamika Bajpai, Ph.D.
Session Name: 201. Granulocytes, Monocytes, and Macrophages: Poster II
Session Date: Sunday, December 10, 2023
Presentation Time: 6:00 – 8:00 PM PT

A copy of each abstract is now available online via the ASH (Free ASH Whitepaper) website at www.hematology.org.

About Chronic Graft-Versus-Host Disease

Chronic graft-versus-host disease (GVHD), an immune response of the donor-derived hematopoietic cells against recipient tissues, is a serious, potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation which can last for years. Chronic GVHD is estimated to develop in approximately 40% of transplant recipients and affects approximately 14,000 patients in the U.S.1,2. Chronic GVHD typically manifests across multiple organ systems, with skin and mucosa being commonly involved, and is characterized by the development of fibrotic tissue3.

About Axatilimab

Axatilimab is an investigational monoclonal antibody that targets colony stimulating factor-1 receptor, or CSF-1R, a cell surface protein thought to control the survival and function of monocytes and macrophages. In pre-clinical models, inhibition of signaling through the CSF-1 receptor has been shown to reduce the number of disease-mediating macrophages along with their monocyte precursors, which has been shown to play a key role in the fibrotic disease process underlying diseases such as chronic GVHD and idiopathic pulmonary fibrosis (IPF). Axatilimab was granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with chronic GVHD and IPF. In September 2021, Syndax and Incyte entered into an exclusive worldwide co-development and co-commercialization license agreement for axatilimab. Axatilimab is being developed under an exclusive worldwide license from UCB entered into between Syndax and UCB in 2016.

About AGAVE-201

The global Phase 2 AGAVE-201 dose-ranging trial evaluated the efficacy, safety, and tolerability of axatilimab in 241 adult and pediatric patients with recurrent or refractory active chronic GVHD whose disease had progressed after two prior therapies. Patients were randomized to one of three treatment groups that investigated a distinct dose of axatilimab administered at 0.3 mg/kg every two weeks, 1 mg/kg every two weeks or 3 mg/kg every four weeks. The trial’s primary endpoint is the proportion of patients in each dose group who achieved an objective response as defined by 2014 NIH Consensus Criteria for chronic GVHD by cycle 7 day 1. Secondary endpoints include duration of response, percent reduction in daily steroids dose, organ specific response rates and validated quality-of-life assessments using the Modified Lee Symptom Scale.

For more information about AGAVE-201, visit View Source

On November 2, 2023 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported third quarter financial results for the period ended September 30, 2023 and provided an update on recent business highlights (Press release, SpringWorks Therapeutics, NOV 2, 2023, View Source [SID1234636795]).

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 continue to work closely with the FDA as they complete their review of our nirogacestat NDA and are ready to serve the desmoid tumor community following an approval," said Saqib Islam, Chief Executive Officer of SpringWorks. "We are also on track to report topline data from our Phase 2b ReNeu trial of mirdametinib in patients with NF1-PN, which, if positive, would position us to file an NDA in the first half of 2024. Together, these anticipated milestones position us to have two medicines approved to treat patients with two distinct devastating diseases. In addition to these near-term events, we continue to advance our broader targeted oncology pipeline, which includes rare oncology, BCMA combinations in multiple myeloma, and biomarker-defined metastatic solid tumor programs, and look forward to providing further updates on our progress over the coming months."

Recent Business Highlights and Upcoming Milestones

Rare Oncology

The Prescription Drug User Fee Act (PDUFA) target action date for the New Drug Application (NDA) for nirogacestat for the treatment of adults with desmoid tumors is November 27, 2023. SpringWorks expects to file a Marketing Authorisation Application for nirogacestat with the European Medicines Agency (EMA) in the first half of 2024.
In November 2023, additional data from the Phase 3 DeFi trial evaluating the impact of nirogacestat on functional status in patients with desmoid tumors were presented at the 2023 Connective Tissue Oncology Society (CTOS) Annual Meeting. Statistically significant and clinically meaningful improvements in physical and role functioning were observed in patients receiving nirogacestat compared with those who received placebo by Cycle 10 across the three prespecified assessment tools evaluated. Patients receiving nirogacestat were five times more likely to have a clinically meaningful improvement in physical functioning and two times more likely to have a clinically meaningful improvement in role functioning compared to placebo at Cycle 10. These improvements began as early as Cycle 2 (the first post-treatment timepoint) and were sustained through Cycle 24 (the final assessment). Improvements in functioning were consistent with the improvements in pain measures, disease-related symptoms, and overall health-related quality of life that were previously reported with nirogacestat.
The ongoing Phase 2 trial evaluating nirogacestat as a monotherapy in patients with recurrent ovarian granulosa cell tumors is fully enrolled. SpringWorks expects to report initial data from the trial in 2024.
SpringWorks expects to present topline data from the pediatric and adult cohorts of the Phase 2b ReNeu trial evaluating mirdametinib, an investigational MEK inhibitor, in NF1-associated plexiform neurofibromas (NF1-PN) in the fourth quarter of 2023. If these data are positive, SpringWorks plans to submit an NDA to the FDA for mirdametinib for the treatment of NF1-PN in the first half of 2024.

B-cell Maturation Antigen (BCMA) Combinations in Multiple Myeloma

SpringWorks continues to evaluate nirogacestat as part of several BCMA combination therapy regimens across treatment lines in collaboration with industry leaders.
In September 2023, the first patient was dosed in the Regeneron-sponsored Phase 1b study arm evaluating nirogacestat in combination with Regeneron’s linvoseltamab, a bispecific antibody targeting BCMA and CD3.

Biomarker-Defined Metastatic Solid Tumors

The dose expansion portion of the Phase 1b trial evaluating brimarafenib (BGB-3245) is ongoing in adult patients with RAF mutant solid tumors. Brimarafenib is an investigational, selective RAF dimer inhibitor being developed by MapKure, LLC, a joint venture between SpringWorks and BeiGene, Ltd.
Patients continue to be enrolled in the dose escalation phase of the SpringWorks-sponsored Phase 1/2a combination study of brimarafenib and mirdametinib.
In August 2023, MapKure filed an Investigational New Drug Application (IND) for a combination study of brimarafenib with panitumumab, a monoclonal antibody targeting EGFR, in colorectal and pancreatic cancer patients with known MAPK pathway mutations and expects to initiate a Phase 1/2a study in the first quarter of 2024. Amgen Inc. is supplying panitumumab pursuant to a clinical trial collaboration agreement with MapKure.
Dose expansion cohort is ongoing in the BeiGene-sponsored Phase 1b/2 trial evaluating mirdametinib in combination with BeiGene’s RAF dimer inhibitor, lifirafenib, in adult patients with NRAS mutant solid tumors.
In September 2023, preclinical data were published in Molecular Cancer Therapeutics characterizing SWTX-143, a TEAD inhibitor tool compound, and describing the potential of TEAD inhibitors to treat multiple Hippo-mutant solid tumor types. SpringWorks plans to file an IND for SW-682, the Company’s TEAD inhibitor development candidate, in the fourth quarter of 2023.

General Corporate

In September 2023, SpringWorks appointed Tai-An Lin, Ph.D., as Chief Scientific Officer. Dr. Lin brings more than 25 years of biotechnology and global pharmaceutical experience in advancing drug discovery programs from target identification through early clinical trials across the therapeutic areas of oncology, immuno-oncology, and immunology.

Third Quarter 2023 Financial Results

Research and Development (R&D) Expenses: R&D expenses were $37.5 million for the third quarter, compared to $36.1 million for the comparable period of 2022. The increase in R&D expenses was primarily attributable to an increase in internal costs driven by the growth in employee costs associated with increases in the number of personnel, including an increase in stock-based compensation expense, partially offset by a decrease in external costs related to drug manufacturing, clinical trials and other research.
General and Administrative (G&A) Expenses: G&A expenses were $46.5 million for the third quarter, compared to $35.7 million for the comparable period of 2022. The increase in G&A expenses was largely attributable to commercial readiness activities to support the U.S. launch of nirogacestat, if approved, for the treatment of adults with desmoid tumors.
Net Loss Attributable to Common Stockholders: SpringWorks reported a net loss of $79.4 million, or $1.27 per share, for the third quarter of 2023. This compares to a net loss of $72.4 million, or $1.37 per share, for the comparable period of 2022.
Cash Position: Cash, cash equivalents and marketable securities were $422.4 million as of September 30, 2023.

On November 2, 2023 Seres Therapeutics, Inc. (Nasdaq: MCRB), a leading microbiome therapeutics company, reported financial results for the third quarter ended September 30, 2023, including VOWST net sales of $7.6 million (Press release, Seres Therapeutics, NOV 2, 2023, View Source [SID1234636794]). Third quarter VOWST commercial results show strong continued progress, driven by a significant increase in new patient starts and exceeding the Company’s forecasted expectations across multiple dimensions. VOWST is indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in adults following antibacterial treatment for recurrent CDI (rCDI) and is commercialized by Nestlé Health Science in collaboration with Seres.

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!

"With a broad label and compelling clinical profile, the launch of VOWST is off to a great start, exceeding our sales expectations. Performance metrics from this first full quarter of launch support our belief that the product is on track to deeply penetrate the rCDI market and fundamentally transform how this disease is managed," said Eric Shaff, President and Chief Executive Officer at Seres.

The Company also announced that it will pursue a strategic restructuring to focus its business operations to prioritize the commercialization of VOWST and the completion of the SER-155 Phase 1b study, while significantly reducing costs and supporting longer-term business sustainability. The Company expects the restructuring, which includes a reduction in the current workforce of 41%, to result in annual cash savings of approximately $75-$85 million in 2024, excluding any one-time charges primarily associated with the workforce reduction.

"Following a thorough review of the Company, we have decided to implement a significant corporate restructuring to substantially reduce expenses and prioritize the commercialization of VOWST. Given the realities of this challenging financial environment for biopharmaceutical companies, we believe that concentrating our resources on VOWST offers an attractive opportunity for targeted revenue growth, while operating in a more capital efficient manner. We will also support our ongoing SER-155 Phase 1b study to an anticipated clinical dataset, expected in the third quarter of 2024. These pending data could extend the highly encouraging early study results that we have already reported. If favorable, these results will provide another potential opportunity to create value for all stakeholders, especially patients."

Mr. Shaff concluded, "Seres’ talented team has been at the forefront of microbiome therapeutics for over a decade and has been responsible for the construction of an unprecedented microbiome platform and knowledge base. We are deeply appreciative of the dedication and valuable contributions of our colleagues who have tirelessly worked and successfully brought our first important medicine to patients in need."

VOWST Performance

Broad demand for VOWST has been observed across both recurrent patients and healthcare providers during the first four months of launch (metrics noted below as provided by Nestlé Health Science through September 30, 2023):

•
1,513 completed prescription enrollment forms for VOWST were received, including 1,215 in the third quarter; of those 934 have culminated in new patient starts, including 837 in the third quarter.

•
Prescription enrollment forms have been submitted by 698 unique healthcare providers (HCPs) since launch, with approximately 70% from gastroenterology and the remainder from other specialties; 129 HCPs have prescribed VOWST to more than one patient.

•
VOWST demand has been observed across the recurrent CDI patient pool, including first recurrence, which is the largest rCDI patient segment.

Key Elements of the Restructuring

Seres is prioritizing the commercial launch of VOWST and continued production capabilities and capacity to support its growth. The Company has implemented operational efficiencies related to the VOWST manufacturing process, providing cost savings, expanding upon actions begun earlier this year. Seres will support the ongoing SER-155 Phase 1b study through its anticipated clinical dataset in the third quarter of 2024.

Seres is significantly scaling back all non-partnered R&D programs and activities other than the completion of the SER-155 Phase 1b study. The Company maintains extensive proprietary microbiome therapeutic drug development capabilities and know-how that may be used to support future R&D efforts. These include proprietary capabilities related to microbiome biomarker discovery, consortia design, pharmacological validation, and advanced manufacturing techniques. In addition, Seres owns a valuable intellectual property estate related to the discovery, development, and manufacture of microbiome therapeutics.

Workforce Reduction: Seres is reducing its workforce by 41% across the organization, which will result in the elimination of approximately 160 positions.

Expected Cost Savings: The workforce reduction and other cost-saving measures, including significantly scaling back all non-partnered research and development activities and reducing general and administrative expenses, are expected to result in annual cash savings of approximately $75-$85 million in 2024, excluding any one-time charges. Seres anticipates incurring a one-time charge of $5.0-$5.5 million in the fourth quarter of 2023, primarily related to the workforce reduction.

Cash Runway: The restructuring is expected to yield significant savings for the Company and position it for longer-term business sustainability. Seres anticipates that its cash, cash equivalents and investments balance as of September 30, 2023, of $169.9 million, in conjunction with the anticipated savings from the restructuring and the expected receipt of the $45 million Tranche B under its existing senior secured debt facility (the Term Loan Facility) with Oaktree Capital Management, L.P. (Oaktree) will support its operations into the fourth quarter of 2024. The Company is eligible for Tranche B under the Term Loan Facility upon the achievement of trailing 6-month VOWST net sales of at least $35 million, no later than September 30, 2024, and other applicable conditions.

Financial Results

Seres reported a net loss of $47.9 million for the third quarter of 2023, as compared with a net loss of $60.0 million for the same period in 2022. Net sales of VOWST for the third quarter of 2023, the first full quarter following launch, were $7.6 million based on 506 units. Following the first commercial sale of VOWST, Seres shares equally with Nestle, its collaborator, in the VOWST commercial profits and losses. Seres’ share of the VOWST net loss for the third quarter of 2023 was $6.5 million, which was included in the Company’s operating results within Collaboration (profit) loss sharing—related party.

Research and development expenses for the third quarter of 2023 were $28.3 million, compared with $43.1 million for the same period in 2022. The research and development expenses were primarily related to Seres’ VOWST clinical development program and manufacturing costs, as well as personnel costs. The year-over-year decrease in R&D expenses is primarily driven by VOWST commercial manufacturing costs no longer being recognized in the Seres P&L following the product approval in April 2023, but instead capitalized and recognized on the Company’s balance sheet.

General and administrative expenses for the third quarter of 2023 were $20.0 million, compared with $18.4 million for the same period in 2022. General and administrative expenses were primarily related to personnel expenses, professional fees, including VOWST commercial readiness and pre-launch expenses incurred prior to the launch of VOWST in June 2023, and facility costs.

Seres ended the third quarter of 2023 with $169.9 million in cash, cash equivalents and investments as compared with $181.3 million at the end of 2022.

Conference Call Information

Seres’ management will host a conference call today, November 2, 2023, at 8:00 a.m. ET. The conference call may be accessed by calling 1-866-777-2509 (international callers dial 1-412-317-5413). To join the live webcast, please visit the "Investors and News" section of the Seres website at www.serestherapeutics.com. A webcast replay will be available on the Seres website beginning approximately two hours after the event and will be archived for at least 21 days.

INDICATION AND IMPORTANT SAFETY INFORMATION FOR VOWST INDICATION

VOWST is indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in individuals 18 years of age and older following antibacterial treatment for recurrent CDI (rCDI).

Limitation of Use: VOWST is not indicated for treatment of CDI.

IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS

Transmissible infectious agents: Because VOWST is manufactured from human fecal matter, it may carry a risk of transmitting infectious agents. Report any infection that is suspected to have been transmitted by VOWST to Aimmune Therapeutics, Inc. at 1-833-246-2566.

Potential presence of food allergens: VOWST may contain food allergens. The potential to cause adverse reactions due to food allergens is unknown.

ADVERSE REACTIONS

The most common adverse reactions (reported in ≥5% of participants) were abdominal distension (31.1%), fatigue (22.2%), constipation (14.4%), chills (11.1%), and diarrhea (10.0%).

To report SUSPECTED ADVERSE REACTIONS, contact Aimmune Therapeutics at 1-833-AIM-2KNO (1-833-246-2566), or the FDA at 1-800-FDA-1088, or visit www.fda.gov/MedWatch.

DRUG INTERACTIONS

Do not administer antibacterials concurrently with VOWST.

Please see Full Prescribing Information and Patient Information

On November 2, 2023 Seagen Inc. (NASDAQ: SGEN) reported that 12- and 24-month progression free survival data will be presented for an ADCETRIS (brentuximab vedotin) and immunotherapy combination in early and advanced stage classical Hodgkin lymphoma (cHL), respectively (Press release, Seagen, NOV 2, 2023, View Source [SID1234636793]). The data will be featured in two oral presentations at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, taking place December 9-12, 2023 in San Diego. The ongoing Phase 2 clinical trial, SGN35-027, is evaluating ADCETRIS in combination with immunotherapy and chemotherapy.

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!

In addition, pre-clinical data will be presented for a next-generation novel CD30-directed antibody-drug conjugate (ADC), SGN-35C, that uses a topoisomerase I inhibitor payload.

"These new data highlight our continued research and development focus on novel combinations to treat Hodgkin lymphoma and on next-generation CD30-directed therapies that aim to further improve outcomes while reducing treatment burden for patients," said Roger Dansey, M.D., President, Research and Development and Chief Medical Officer at Seagen.

ADCETRIS is a proven foundation of care for certain CD30-expressing lymphomas with more than 120,000 patients treated globally across seven indications.

Key data for Seagen at ASH (Free ASH Whitepaper) include:

Presentations of Company-Sponsored Trials

Abstract Title

Abstract #

Presentation

Lead Author

Brentuximab vedotin

Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced stage classical Hodgkin lymphoma: efficacy and safety results from the single arm phase 2 study (SGN35-027 Part B)

608

Oral 624

Sunday, Dec. 10

4:45 p.m. PT

Grand Hall B

Lee

Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine (AN+AD) for early-stage classical Hodgkin lymphoma (SGN35-027 Part C)

611

Oral 624

Sunday, Dec. 10

5:30 p.m. PT

Grand Hall B

Abramson

Brentuximab vedotin in frontline therapy of Hodgkin lymphoma in patients with significant comorbidities ineligible for standard chemotherapy (SGN35-015 Part E)

4435

Poster

Monday, Dec. 11

6:00 – 8:00 p.m. PT

Halls G-H

Yasenchak

PET4 response as an independent predictor of long-term outcomes in ECHELON-2 A+CHP vs CHOP in CD30+PTCL

3074

Poster

Sunday, Dec. 10

6:00 – 8:00 p.m. PT

Halls G-H

Iyer

The comparative effectiveness of A+AVD vs PET-guided ABVD for the management of patients with advanced Hodgkin lymphoma: a systematic review and matching-adjusted indirect treatment comparison (Takeda sponsored)

1713

Poster

Saturday, Dec. 9

5:30 – 7:30 p.m. PT

Halls G-H

Kristo

Real-world treatment patterns and patient outcomes in relapsed/refractory Hodgkin lymphoma in the US (Takeda sponsored)

–

Abstract only

Kristo

Early-Stage/Pipeline

SGN-35C: a novel CD30-directed antibody-drug conjugate for the treatment of lymphomas

1440

Poster

Saturday, Dec. 9

5:30 – 7:30 p.m. PT

Halls G-H

Hamblett

Presentations of Investigator and Cooperative Group-Sponsored Trials

Abstract Title

Abstract #

Presentation

Lead Author

Brentuximab vedotin

Identifying tumor-specific immune response and biomarkers of high-risk Hodgkin lymphoma patients treated with and without brentuximab on Children’s Oncology Group trial AHOD1331

4383

Poster, Monday, Dec. 11

6:00 – 8:00 p.m. PT

Halls G-H

Toner

Longitudinal differences by treatment arm in health-related quality of life among high risk pediatric Hodgkin’s lymphoma patients treated on the Children’s Oncology Group AHOD 1331 study

672

Oral 905

Sunday, Dec. 10

5:54 p.m. PT

Grand Ballroom 2-4

Williams

AHOD2131: a randomized phase 3 response-adapted trial comparing standard therapy with immuno-oncology therapy for children and adults with newly diagnosed stage I and II classic Hodgkin lymphoma

3084

Poster

Sunday, Dec. 10

6:00 – 8:00 p.m. PT

Halls G-H

Henderson

Brentuximab vedotin in combination with nivolumab in CD30+ malignancies refractory to brentuximab vedotin

3060

Poster

Sunday, Dec. 10

6:00 – 8:00 p.m. PT

Halls G-H

Poh

Reduced dose brentuximab vedotin for mycosis fungoides appears to prolong response duration by balancing efficacy and tolerability

1702

Poster Saturday, Dec. 9

5:30 – 7:30 p.m. PT

Halls G-H

Munayirji

Final results of a multicenter pilot study evaluating brentuximab vedotin with cyclophosphamide, doxorubicin, etoposide, and prednisone (BV-CHEP) for the treatment of aggressive adult T-cell leukemia/lymphoma

1692

Poster

Saturday, Dec. 9

5:30 – 7:30 p.m. PT

Halls G-H

Dittus

Immune landscape associated with response to brentuximab vedotin with ipilimumab and/or nivolumab in relapsed/refractory Hodgkin lymphoma (E4412 phase 1)

4382

Poster

Monday, Dec. 11

6:00 – 8:00 p.m. PT

Halls G-H

Gonzalez-Kozlova

CNS involvement in pediatric Hodgkin lymphoma: a comprehensive retrospective analysis from the SEARCH for CAYAHL group

3066

Poster

Sunday, Dec. 10

6:00 – 8:00 p.m. PT

Halls G-H

Pabari

Comprehensive analysis of treatment related morbidity and progression-free survival in the GHSG phase III HD21 trial

3057

Poster

Sunday, Dec. 10

6:00 – 8:00 p.m. PT

Halls G-H

Borchmann

Pregnancies and childbirth following advanced-stage HL treatment with BrECADD or BEACOPP in the randomized phase III GHSG HD21 trial

4437

Poster

Monday, Dec. 11 6:00-8:00 p.m.

Halls G-H

Ferdinandus

About ADCETRIS

ADCETRIS is an antibody-drug conjugate (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.