On October 28, 2022 Flare Therapeutics, a biotechnology company targeting transcription factors to discover precision medicines for cancer and other diseases, reported that translational insights from a retrospective advanced urothelial cancer (UC) cohort in a poster titled, "Peroxisome Proliferator-Activated Receptor Gamma (PPARG) status defines the luminal lineage in molecular profiles of advanced urothelial cancers (UC)" at the 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium, being held in Barcelona, Spain (Press release, Flare Therapeutics, OCT 28, 2022, View Source [SID1234622586]). Molecular RWD, comprising of more than 3,000 genomic and transcriptomic profiles from advanced UC tissue, were utilized to evaluate the transcription factor PPARG, and its role as a master regulator of the luminal lineage associated with its expression and mutational status.

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!

"To the best of our knowledge, this represents the largest RWD from patients with advanced and metastatic urothelial cancer, providing unique insights into the persistence of PPARG signaling through disease progression, independent of the treatment paradigm," said Michaela Bowden, Ph.D., Senior Vice President of Biology and Translation at Flare Therapeutics. "Stratification of patients based upon their PPARG status serves as the foundation for our precision approach in identifying individuals most likely to respond to PPARG inhibition."

Flare presented its novel PPARG program demonstrating robust preclinical activity in a poster presentation titled, "Novel inhibitors of the luminal lineage transcription factor peroxisome proliferator-activated receptor gamma (PPARG) durably eradicate tumors in urothelial cancer animal models" on Wednesday, October 26th at same symposium.

Data highlights:

65% of advanced urothelial cancers evaluated were classified as luminal, of which one in three were enriched for genetic alterations in PPARG, RXRA or FGFR3
PPARG amplification, including a gain of only one copy number, is associated with higher PPARG expression
PPARG expression levels were sustained in metastatic lesions compared locally advanced tissues and did not significantly vary by metastatic tissue site
Flare is advancing a novel PPARG inhibitor through Investigational New Drug (IND)-enabling studies and expects to initiate its Phase 1 clinical trial in 2023 in individuals with locally advanced or metastatic UC.

About Advanced Urothelial Cancer
Muscle-invasive UC is a common type of bladder cancer, with about 20,000 individuals diagnosed each year in the United States alone, and significantly higher incidence rates in other regions of the world. This disease has high rates of recurrence and the five-year survival rate is approximately 5% in metastatic cases. The transcription factor peroxisome proliferator-activated receptor gamma (PPARG) is associated with the luminal lineage subtype reflecting approximately 65% of all advanced UC patients. Recurrent genetic alterations in PPARG, including focal amplification, missense mutations, and fusions, as well as hotspot mutations in its binding partner, retinoid X receptor alpha (RXRA) are characteristic of this molecular subtype.

On October 28, 2022 Exscientia plc (Nasdaq: EXAI) reported that the company has won the Prix Galien USA 2022 Award for Best Digital Health Solution in recognition of its AI-driven precision medicine platform (Press release, Exscientia, OCT 28, 2022, View Source [SID1234622585]). The award was presented Thursday at the Prix Galien Forum in New York City. Worldwide, the Prix Galien, which recognizes excellence in scientific innovation that improves the state of human health, is regarded as the most coveted prize in biopharmaceutical research.

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!

Exscientia is focused on designing fundamentally better drugs – faster. The company’s artificial intelligence (AI)-driven functional precision medicine platform enables a "patient-first" approach by integrating primary human tissue samples into early target and drug discovery research. Earlier this year, the next-generation platform, which aims to reinvent the way drugs are discovered and developed, was clinically proven to guide treatment selection and improve cancer treatment outcomes, in the landmark EXALT-1 study.

EXALT-1 demonstrated the ability of one of Exscientia’s AI-discovered medicines to improve cancer treatment outcomes, marking the first time a functional precision oncology platform improved patient outcomes in an interventional clinical study. Today, the live tissue technology used in that study is a core component underpinning Exscientia’s end-to-end platform, which has discovered the first three AI-designed molecules to enter clinical trials, dramatically cutting the time and cost required to generate novel molecules with the potential to become approved medicines.

"Sincere thanks to the Galien Foundation and Business France for this incredible honour. Exscientia is humbled to receive this recognition and grateful to our incredible team whose vision made it possible," said Exscientia founder and CEO Andrew Hopkins, DPhil. "This award is a recognition of the enormous potential that AI holds to transform how our industry discovers and develops the right drug for the right patient. This award recognized the potential of our AI driven precision medicine platform to truly bring the vision of personalised medicine to the benefit of the patient. The day is coming when all medicines will be discovered and developed by harnessing the power of AI. At Exscientia, we are proud to be pioneering the way forward."

On October 28, 2022 AC Immune SA (NASDAQ: ACIU), a clinical-stage biopharmaceutical company pioneering precision medicine for neurodegenerative diseases, reported that results for the third quarter ended September 30, 2022, and provided a corporate update (Press release, AC Immune, OCT 28, 2022, View Source [SID1234622584]).

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!

Prof. Andrea Pfeifer, CEO of AC Immune SA, commented: "With the recent positive data for an anti-Abeta antibody, lecanemab, further supporting the amyloid hypothesis in Alzheimer’s disease (AD), we are advancing towards year-end with strong momentum and renewed enthusiasm for the amazing potential of our development programs. The recent data also highlight the importance of intervening early in AD, further underlining the fundamental need for precision medicine in neurodegenerative diseases. This bodes well for our wholly owned vaccine ACI-24.060, which targets the two most toxic forms of Abeta, soluble toxic Abeta oligomers and pyroglu-Abeta. Because ACI-24.060 is a vaccine, it also has the potential to offer safety, efficacy, and logistical advantages compared to monoclonal antibodies. A key Phase 1b readout from ACI-24.060’s translational, biomarker-based trial is planned later this year, and is expected to inform our advancement into Phase 2 cohorts in AD and Down syndrome-related AD."

"Our cutting-edge diagnostic programs also received key external validation last quarter, with our partner Life Molecular Imaging announcing initiation of late-stage clinical development of our Tau PET tracer – triggering a milestone payment. The Michael J. Fox Foundation (MJFF) also recognized our alpha-synuclein (a-syn) tracer with a follow-on grant to develop a-syn PET tracers that could accelerate clinical development. These accomplishments affirm our leadership and commitment to leveraging precision medicine to enable earlier diagnosis, treatment, and ultimately prevention of neurodegenerative disease."

Q3 2022 and Subsequent Highlights

Detailed results from the Phase 2 Alzheimer’s Prevention Initiative (API) study evaluating the anti-Abeta monoclonal antibody crenezumab in autosomal dominant Alzheimer’s disease (ADAD) were presented at the 2022 Alzheimer’s Association International Conference (AAIC) by AC Immune’s partner Genentech, a member of the Roche group, and the Banner Alzheimer’s Institute. Numerical differences favoring crenezumab were observed across both co-primary endpoints, as well as multiple secondary and exploratory endpoints, though none were statistically significant. Demographic and baseline biomarker data indicate a confluence of factors may have led the study to have lower than expected statistical power. All mutation carriers in the study may continue to receive crenezumab while the data are further analyzed.
Provided an update on the Phase 1b/2 ABATE study of the anti-Abeta vaccine ACI-24.060 in patients with prodromal AD and individuals with Down syndrome (DS). Clinical sites in the UK and Spain are now open and recruiting following regulatory clearances in both countries. Interim results are expected around year end 2022 with plans to submit a U.S. Investigational New Drug (IND) application in Q1 2023.
Received clearance for a clinical trial application to initiate an adaptive, biomarker-based Phase 2 study of the anti-a-syn vaccine ACI-7104 in patients with early Parkinson’s disease (PD). Initiation of the trial is expected in Q4 2022.
The Tau PET tracer, PI-2620, is being advanced into late-stage development in AD by our partner, Life Molecular Imaging, following supportive results from an investigator-sponsored Phase 2 AD trial that showed its suitability as a targeted radiopharmaceutical for the detection of Tau deposits and for measuring longitudinal changes in subjects with mild cognitive impairment (MCI) as well as in patients with AD.
Received a MJFF follow-on grant to support the continued development of ACI-12589, AC Immune’s wholly-owned a-syn PET tracer. The new grant brings the total MJFF funding for this program up to USD 3.7 million.
Showcased pipeline of potentially first- and best-in-class therapeutic and diagnostic candidates with 10 presentations at the AAIC.
First-time presentation at AAIC of a biomarker-based, translational clinical trial of AC Immune’s wholly owned anti-Abeta vaccine, ACI-24.060, in patients with AD and individuals with DS.
Hosted a key opinion leader webinar on the potential benefits of vaccines for Alzheimer’s and Parkinson’s diseases. The webinar featured a presentation by Cynthia A. Lemere, Ph.D., of the Ann Romney Center for Neurologic Diseases at Brigham & Women’s Hospital and Harvard Medical School. To view a replay of the webinar, click here.
Achieved and Anticipated 2022 Clinical Milestones

ACI-24.060
anti-Abeta vaccine Dosed first patient in Phase 1b/2 ABATE study of ACI-24.060 in patients with AD and individuals with DS.
Phase 1b safety and immunogenicity data readout in AD and decision to move into DS expected in Q4 2022. Submission of U.S. Investigational New Drug (IND) application planned in Q1 2023.
ACI-35.030
anti-pTau vaccine Reported Phase 1b/2a interim analysis from highest dose group.
Expect the decision to move into late-stage development in Q4 2022.
ACI-7104
anti-a-syn vaccine Initiation of Phase 2 trial in early PD expected in Q4 2022.
Crenezumab
anti-Abeta antibody Reported detailed results from Phase 2 API-ADAD study in autosomal dominant AD.
Additional fluid biomarker data to be presented at CTAD 2022 Conference
Semorinemab
anti-Tau antibody Additional biomarker data from the Phase 2 Lauriet study in mild-to-moderate AD expected at CTAD 2022 Conference.
ACI-12589
a-syn-PET tracer Reported breakthrough results from first-in-human study at AD/PD 2022 conference.
PI-2620
Tau-PET tracer Reported Phase 2 results in AD enabling entry into late-stage development connected to a milestone payment.
Clinical PET study data in orphan indication in Q4 2022.

Analysis of Financial Statements for the Quarter Ended September 30, 2022

Cash Position: The Company had a total cash balance of CHF 140.5 million, composed of CHF 44.5 million in cash and cash equivalents and CHF 96.0 million in short-term financial assets. This compares to a total cash balance of CHF 198.2 million as of December 31, 2021. The Company’s cash balance provides cash for operations into Q3 2024 without consideration of potential incoming milestone payments.

R&D Expenditures: R&D expenses decreased by CHF 0.7 million for the three months ended September 30, 2022, to CHF 14.4 million.

Discovery and preclinical expenses (- CHF 0.8 million): The Company decreased expenditures across a variety of its discovery and preclinical programs.

Clinical expenses (- CHF 0.6 million): The Company’s increased expenditures for the accelerated clinical development programs of ACI-7104 and ACI-24.060 were offset by lower costs in various other clinical programs as they achieved anticipated goals.

Other non-allocated (+ CHF 0.5 million): The Company’s other non-allocated R&D expenditure increased by CHF 0.5 million mostly related to the reallocation of certain IT and facilities costs and IT investments.

G&A Expenditures: For the three months ended September 30, 2022, G&A decreased by CHF 2.1 million to CHF 3.3 million. This decrease is mostly related to the reallocation of certain IT and facilities expenditures made in Q3 2022 that were not reclassified in the prior period and the reversal of certain share-based compensation expenses.

Other Operating Income: The Company recognized CHF 0.3 million in grant income for R&D activities performed under our Michael J. Fox Foundation for Parkinson’s Research (MJFF) and Target ALS grants, an increase of less than CHF 0.1 million compared to the prior period.

IFRS Loss for the Period: The Company reported a net loss after taxes of CHF 13.5 million for the three months ended September 30, 2022, compared with a net loss of CHF 15.9 million for the comparable period in 2021.

On October 28, 2022 Genmab A/S (Nasdaq: GMAB) reported that the company has submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for subcutaneous epcoritamab (DuoBody-CD3xCD20), an investigational bispecific antibody, for the treatment of patients with relapsed/refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy (Press release, Genmab, OCT 28, 2022, View Source [SID1234622579]). Additionally, Genmab announced that AbbVie (NYSE: ABBV) submitted a Marketing Authorization Application (MAA) for epcoritamab for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy, which has been validated by the European Medicines Agency (EMA).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The regulatory submissions are supported by previously announced results from the LBCL cohort of the pivotal EPCORE NHL-1 open-label, multi-center phase 2 clinical trial evaluating the safety and preliminary efficacy of epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin lymphoma (B-NHL), including DLBCL. These results were presented in a late-breaking oral presentation as a part of the Presidential Symposium at the 27th Annual Meeting of the European Hematology Association (EHA) (Free EHA Whitepaper) (EHA2022), on June 11, 2022, in Vienna, Austria.

"Even with existing therapies to treat these lymphomas, there is a significant medical need for alternative and accessible treatment options for patients who are unable to tolerate current treatments or whose treatments have failed," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "Together with our partner AbbVie, we believe epcoritamab has the potential to become a core therapy for patients with B-cell malignancies, and the submission of these regulatory applications to the FDA and EMA is an important step in potentially bringing epcoritamab to people living with relapsed/refractory B-cell lymphomas."

Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. The companies are committed to evaluating epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies, including an ongoing phase 3, open-label, randomized clinical trial evaluating epcoritamab as a monotherapy in patients with relapsed/refractory DLBCL (NCT: 04628494) and a phase 3, open-label clinical trial evaluating epcoritamab in combination in patients with relapsed/refractory follicular lymphoma (FL) (NCT: 05409066).

About Large B-cell Lymphoma (LBCL) and Diffuse Large B-cell Lymphoma (DLBCL)
Large B-cell lymphoma (LBCL) is a fast-growing type of non-Hodgkin’s lymphoma (NHL), a cancer that develops in the lymphatic system and affects B-cell lymphocytes, a type of white blood cell. There are an estimated 150,000 new LBCL cases each year globally.1,2 Diffuse large B-cell lymphoma (DLBCL) is a fast-growing type of NHL3 and the most common type of NHL worldwide, accounting for approximately 31 percent of all NHL cases.2 DLBCL can arise in lymph nodes as well as in organs outside of the lymphatic system, occurs more commonly in the elderly and is slightly more prevalent in men.1

About the EPCORE NHL-1 Trial
EPCORE NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab including a phase 1 first-in-human, dose escalation part; a phase 2 expansion part; and an optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-NHL, including LBCL and DLBCL. Data from the dose escalation part of the study, which determined the recommended phase 2 dose, were published in The Lancet in 2021. In the phase 2 expansion part, additional patients are treated with epcoritamab to further explore the safety and efficacy of epcoritamab in patients with different types of relapsed/refractory B-NHLs who had limited therapeutic options.

The primary endpoint of the phase 2 expansion part was overall response rate (ORR) as assessed by an IRC. Secondary efficacy endpoints included duration of response, complete response rate, progression-free survival, overall survival, time to response, time to next therapy, and rate of minimal residual disease negativity.

About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response towards target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B-cells and induces T cell mediated killing of CD20+ cells.4 CD20 is expressed on B-cells and a clinically validated therapeutic target in many B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.5,6

On October 28, 2022 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported findings from a retrospective pooled analysis of patients who achieved extended treatment benefit (ETB) with mirvetuximab soravtansine (mirvetuximab) monotherapy across three clinical trials in folate receptor alpha (FRα)–positive recurrent ovarian cancer (Press release, ImmunoGen, OCT 28, 2022, View Source [SID1234622578]). These findings were highlighted in a poster presentation at the 23rd Congress of the European Society of Gynaecological Oncology (ESGO) in Berlin, Germany. A trial in progress poster from the mirvetuximab program will also be presented.

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 believe the study outcomes presented at ESGO support the potential benefit mirvetuximab can have for a subset of patients on a long-term basis and add to the strong, existing foundation of data that supports mirvetuximab’s potential to become the new standard of care for FRα-positive ovarian cancer," said Anna Berkenblit, MD, Senior Vice President and Chief Medical Officer of ImmunoGen. "With the PDUFA date for mirvetuximab rapidly approaching, we look forward to the opportunity to bring this novel therapy to patients before the end of this year."

CHARACTERIZATION OF EXTENDED TREATMENT BENEFIT FROM THREE PHASE 1 AND 3 CLINICAL TRIALS EXAMINING PATIENTS WITH FOLATE RECEPTOR ALPHA–POSITIVE RECURRENT OVARIAN CANCER TREATED WITH SINGLE-AGENT MIRVETUXIMAB SORAVTANSINE
Lead Author: Ana Oaknin, MD
Date/Time: October 28, 2022, 2:40 – 3:40 PM CET / 8:40 – 9:40 AM ET
Poster: #PA-048

A retrospective pooled analysis of patients who achieved ETB with mirvetuximab monotherapy was conducted across three studies – the Phase 1 IMGN853-0401 trial, the Phase 3 FORWARD I trial, and the Phase 3 SORAYA trial. ETB was defined as progression-free survival (PFS) for more than 12 months per investigator assessment. FRα expression levels were evaluated by immunohistochemistry (IHC).

Key findings:

In a pooled analysis of 466 patients, mirvetuximab monotherapy demonstrated ETB in 40 patients (9%).
Most patients with ETB had stage III disease (83%), 1 prior line of therapy (55%), and prior Avastin (bevacizumab) exposure (60%).
EBT occurred in patients with a wide range of FRα expression, but did so predominantly among those with high FRα expression.
Patients with ETB had an objective response rate (ORR) of 77.5% (31 out of 40 patients), with 10 (25%) achieving a complete response and 21 (52.5%) achieving a partial response. The remaining 8 patients (20%) with ETB had a best response of stable disease and one patient was not evaluable.
Median duration of response (DOR) in patients with ETB was 22.1 months (95% CI, 13.8-60.0).
Median PFS in patients with ETB was 17.0 months (95% CI, 16.4-23.1).
In patients with ETB, the overall adverse event (AE) profile was consistent with the previously reported integrated safety summary (ISS) of 464 patients, with no new safety signals identified and minimal cumulative toxicities.
AEs were primarily low-grade gastrointestinal and ocular events that generally resolved with supportive care or, if needed, dose modifications.
"Treatment options for patients with platinum-resistant ovarian cancer are extremely limited and characterized by low activity and considerable toxicity," said Ana Oaknin, Head of Gynecologic Tumors Unit,Vall d’Hebron Institute of Oncology, Senior Medical Oncologist and Attending Physician, Medical Oncology Department, Vall d’Hebron University Hospital. "The results from this analysis, coupled with a favorable tolerability and a consistent safety profile, add to the excitement I and many other physicians now have for the potential of mirvetuximab for women with FRα-positive platinum-resistant ovarian cancer."

ADDITIONAL PRESENTATIONS

A trial in progress poster for a randomized Phase 2 investigator-sponsored trial (IST) of mirvetuximab in combination with carboplatin in patients with FRα-high recurrent ovarian cancer will also be presented.

Additional information can be found at www.congress.esgo.org.

ABOUT MIRVETUXIMAB SORAVTANSINE

Mirvetuximab soravtansine is a first-in-class ADC comprising a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells.