On September 28, 2019 G1 Therapeutics, Inc. (Nasdaq: GTHX), a clinical-stage oncology company, today reported preliminary overall survival (OS) data from the company’s randomized Phase 2 trial of trilaciclib in combination with chemotherapy for the treatment of metastatic triple-negative breast cancer (mTNBC) (Press release, G1 Therapeutics, SEP 28, 2019, View Source [SID1234539978]). In the trial, median overall survival for patients treated with trilaciclib in combination with a chemotherapy regimen of gemcitabine/carboplatin (GC) was 20.1 months, compared with 12.6 months for patients receiving chemotherapy alone. These data were reported as part of a late-breaking oral presentation (LBA22) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress and featured in a concurrent publication in The Lancet Oncology.

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!

Updated data from a separate randomized Phase 2 trial of trilaciclib in small cell lung cancer (SCLC) will be presented during a poster session (1742PD) on Sunday, September 29 at ESMO (Free ESMO Whitepaper) 2019 in Barcelona, Spain.

"Triple-negative breast cancer is the most aggressive form of breast cancer and tends to have a poorer prognosis than other breast cancers. We need new therapeutic approaches that improve outcomes for women diagnosed with triple-negative breast cancer," said Joyce A. O’Shaughnessy, M.D., Baylor University Medical Center, Texas Oncology, U.S. Oncology, and lead investigator for the trial. "As an oncologist specializing in triple-negative breast cancer, I am encouraged that trilaciclib has the potential to improve the survival of patients diagnosed with this disease."

"Trilaciclib is a first-in-class therapy that has improved outcomes for people with cancer being treated with chemotherapy in four randomized Phase 2 trials. The findings from these trials in small cell lung cancer and triple-negative breast cancer indicate that the clinical benefits of trilaciclib are meaningful and context-dependent," said Raj Malik, M.D., Chief Medical Officer and Senior Vice President, R&D. "In metastatic triple-negative breast cancer, the benefit manifests as improved overall survival. In small cell lung cancer, patients experience myelopreservation benefits, including reduced rates of neutropenia, anemia and other chemotherapy-related side effects, and a corresponding decrease in the use of rescue therapies required to address those toxicities. Importantly, patient-reported outcome measures across all of our trials showed that trilaciclib improved the patient experience on chemotherapy."

Mark Velleca, M.D., Ph.D., Chief Executive Officer, added: "Based on feedback from our pre-NDA meeting with the FDA, we will begin a rolling NDA submission for small cell lung cancer in the fourth quarter of this year, which we expect to complete in the second quarter of 2020. We have also had initial discussions with the FDA regarding development of trilaciclib in triple-negative breast cancer, including the preliminary design of a Phase 3 trial. In 2020, we plan to initiate a Phase 3 trial in triple-negative breast cancer and a Phase 3 trial in colorectal cancer, with the goal of demonstrating the benefits of trilaciclib to patients receiving chemotherapy for multiple tumor types."

Overall survival benefit in mTNBC

The randomized, open-label Phase 2 study (NCT02978716) of trilaciclib in combination with GC, a current standard of care for TNBC, enrolled 102 patients who had received up to two prior chemotherapy regimens for locally recurrent or metastatic TNBC. In this three-arm trial, all three groups received a chemotherapy regimen of GC. Patients were randomized to receive GC only (Group 1) or GC plus one of two dosing schedules of trilaciclib: trilaciclib administered on the day of chemotherapy (Group 2) or trilaciclib administered the day prior to and the day of chemotherapy (Group 3). Primary endpoints for the trial included myelopreservation measures; secondary endpoints included additional myelopreservation measures and anti-tumor efficacy measures of overall response rate (ORR), progression-free survival (PFS) and OS. Myelopreservation and preliminary anti-tumor efficacy results from the trial were reported at the 2018 San Antonio Breast Cancer Symposium (press release here). Topline OS findings were announced in June 2019 (press release here); detailed OS results were reported for the first time at ESMO (Free ESMO Whitepaper) 2019.

Updated results from the trial showed:

The addition of trilaciclib to chemotherapy resulted in a significant increase in OS in both treatment groups compared to chemotherapy alone.

Compared to GC alone (Group 1), OS was improved for both trilaciclib arms (Groups 2 and 3) with median OS of 12.6 months, 20.1 months and 17.8 months, respectively (Group 2: HR=0.33, p=0.0283; Group 3: HR=0.34, p=0.0023). The median OS for Groups 2 and 3 combined was 20.1 months (HR=0.36, p=0.0015). The median OS for GC alone (Group 1, 12.6 months) was consistent with historical data.

PFS and ORR were consistent with previously reported data.

The safety and tolerability of trilaciclib were consistent with previously reported data.

There have been no serious adverse events attributed to treatment with trilaciclib in this trial.

Patient-reported outcome (PRO) measures related to anemia were improved in patients receiving trilaciclib versus patients receiving chemotherapy alone.

As previously reported, primary endpoints (myelopreservation measures) were not met.

Trilaciclib in SCLC

On Sunday, September 29, G1 Therapeutics will present updated results from its randomized, double-blind, placebo-controlled Phase 2 trial (NCT03041311) evaluating trilaciclib in extensive-stage SCLC patients receiving first-line chemotherapy and the checkpoint inhibitor Tecentriq (atezolizumab). The findings were consistent with previously reported data (press release here):

Trilaciclib demonstrated myelopreservation benefits, as shown by statistically significant and clinically meaningful improvement in reduction of myelosuppression endpoints, reduction of chemotherapy side effects and reduction of rescue interventions.

Trilaciclib was well tolerated, with fewer ³ Grade 3 adverse events (AEs) compared to placebo.

PRO measures related to anemia were improved in patients receiving trilaciclib versus patients receiving placebo.

Trilaciclib did not adversely impact chemotherapy anti-tumor efficacy as measured by ORR, PFS and OS.

Additionally, data from another randomized Phase 1b/2 trial of trilaciclib in patients with SCLC receiving first-line chemotherapy were recently published in Annals of Oncology, the official journal of ESMO (Free ESMO Whitepaper). Data in this trial demonstrated the myelopreservation benefits of trilaciclib as indicated by statistically significant reduction in clinically relevant consequences of myelosuppression compared to placebo, resulting in fewer supportive care interventions and dose reductions. Trilaciclib did not adversely impact the anti-tumor efficacy of chemotherapy.

Webcast and Conference Call Details

G1 Therapeutics will host a webcast and conference call of its investor and analyst event on Sunday, September 29, 2019, at 6:45 p.m. CEST (12:45 p.m. ET) to review the data being presented at ESMO (Free ESMO Whitepaper) 2019, as well as long-range development plans for all three of its clinical-stage therapies and commercial plans for trilaciclib. The live call may be accessed by dialing 866-763-6020 (domestic) or 210-874-7713 (international) and entering the conference code: 5878315. A live and archived webcast will be available on the Events & Presentations page of the company’s website at www.g1therapeutics.com. The webcast will be archived on the same page for 90 days following the event.

About Trilaciclib

Trilaciclib is a first-in-class investigational therapy designed to improve outcomes for people with cancer treated with chemotherapy. Based on results from three randomized trials in patients with small cell lung cancer, trilaciclib has received Breakthrough Therapy Designation, and G1 Therapeutics expects to submit marketing applications in the U.S. and Europe for myelopreservation in small cell lung cancer in 2020. In a randomized trial of women with metastatic triple-negative breast cancer, trilaciclib improved overall survival when administered in combination with chemotherapy compared with chemotherapy alone. The company plans to initiate a Phase 3 clinical trial in triple-negative breast cancer and a Phase 3 clinical trial in colorectal cancer in 2020.

On September 28, 2019 Immunomedics, Inc. (NASDAQ: IMMU) ("Immunomedics" or the "Company"), a leading biopharmaceutical company in the area of antibody-drug conjugates (ADC), reported at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress interim data from the 100-patient cohort of cisplatin-eligible patients of the Company’s TROPHY-U-01 open-label Phase 2 study (Press release, Immunomedics, SEP 28, 2019, View Source [SID1234539913]). In this interim report, sacituzumab govitecan produced an overall response rate (ORR) of 29 percent in 35 patients with metastatic urothelial cancer (mUC) who have relapsed or are refractory to immune checkpoint inhibitors (CPI) and platinum-based 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!

"Patients with mUC who have cancer progression after platinum-based and CPI therapy have poor outcomes and limited treatment options. Together with the prior clinical data, I believe the favorable benefit/risk profile of sacituzumab govitecan has the potential to change the treatment landscape of UC," commented Dr. Scott T. Tagawa, the Richard A. Stratton Associate Professor in Hematology and Oncology, Associate Professor of Clinical Medicine and of Clinical Urology, member of the Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, who presented the interim results from TROPHY-U-01 at the ESMO (Free ESMO Whitepaper) 2019 Annual Congress in Barcelona, Spain.

The 29 percent ORR included two confirmed complete responses, six confirmed partial responses (PRs) and two additional PRs pending confirmation. At the time of data cutoff on August 5, 2019, eight of ten responders have ongoing response. Median time to onset of response was 1.5 months (range, 1.2-2.8). For patients with liver metastases, ORR was 25 percent.

"These interim results, in a larger number of CPI-experienced patients, are consistent with previously reported efficacy of sacituzumab govitecan in mUC, and also show encouraging benefits observed in patients relapsed on enfortumab vedotin," stated Dr. Behzad Aghazadeh, Executive Chairman of Immunomedics. "Based on these data, the Company will be exploring registrational pathways with the FDA."

Consistent with the Company’s previous observations, sacituzumab govitecan was well tolerated with a predictable safety profile. Treatment-related Grade 3 and 4 adverse events were mostly hematologic and gastrointestinal related, including neutropenia (54%) and diarrhea (9%). Importantly, there were no grade 2 or above neuropathy or rash, no interstitial lung disease, and no treatment-related deaths.

New Clinical Collaborations to Advance Sacituzumab Govitecan to Early-Line Treatment of Breast Cancer

In addition, the Company announced two clinical collaborations that address continuing unmet needs in breast cancer. The collaboration with Roche will evaluate the safety and efficacy of the combination of atezolizumab (Tecentriq), a programmed cell death ligand 1 (PD-L1)-blocking checkpoint inhibitor, and sacituzumab govitecan, as a frontline treatment of patients with metastatic or inoperable locally advanced TNBC.

"We are pleased to be partnering with Roche, a global leader in breast cancer therapy," said Dr. Aghazadeh. "With a favorable efficacy and safety profile, we believe sacituzumab govitecan is a strong combination partner and could provide an improved therapeutic option in earlier lines of therapy when combined with immune checkpoint inhibitors."

The open-label, multicenter, randomized Phase 1b/2 study will be conducted as part of MORPHEUS, Roche’s novel cancer immunotherapy development platform. Patients with newly-diagnosed mTNBC will be randomized to receive the combination of atezolizumab and sacituzumab govitecan or nab-paclitaxel plus atezolizumab as standard of care. MORPHEUS is a Phase 1b/2 adaptive platform to develop combinations of cancer immunotherapies more rapidly and efficiently. Roche will be responsible for conducting the randomized trial.

Further, Immunomedics and the GBG Forschungs-GmbH (GBG), Neu-Isenburg, Germany, have entered into a collaboration to develop sacituzumab govitecan as a treatment for newly-diagnosed breast cancer patients who do not achieve a pathological complete response (pCR) following standard neoadjuvant therapy.

"While pCR is now widely accepted as a very strong surrogate endpoint for event-free and distant disease-free survival (DDFS) in high-risk breast cancer, for patients who do not achieve a pCR following standard neoadjuvant therapy, the risk for developing metastatic disease is very high," said Professor Dr. med. Sibylle Loibl, MD, PhD, Chief Executive Officer of GBG. "We are very excited to be the first cooperative group worldwide to evaluate sacituzumab govitecan in this early stage of breast cancer treatment."

According to the medical literature, depending on the hormone receptor status, about 40% to 70% of HER2-negative breast cancer patients treated with neoadjuvant therapy do not achieve a pCR.1 For these patients, with the exception of those with the HER2-positive subtype, there is currently no approved standard of care, leaving them at high risk of distant relapse of their disease.

"We are extremely pleased to partner with GBG, the world-renowned cooperative group, to launch this exciting study which will introduce sacituzumab govitecan to breast cancer patients at an early stage of their disease," commented Dr. Aghazadeh. "We look forward to working closely with GBG to study the potential benefits of sacituzumab govitecan in a significantly larger population of breast cancer patients who have few viable alternatives today."

The multinational, post-neoadjuvant Phase 3 SASCIA study developed by GBG will be conducted under the sponsorship of GBG. Approximately 1,200 high-risk patients with newly-diagnosed HER2-negative breast cancer not achieving a pCR following standard neoadjuvant therapy will be randomized to receive either sacituzumab govitecan or treatment of physician’s choice. Primary endpoint is invasive DFS (iDFS) with overall survival, patient reported outcome/quality of life, circulating tumor DNA clearance, and safety serving as secondary endpoints.

"Given the high level of Trop-2 expression in breast cancer, we are hopeful that sacituzumab govitecan will be established as a new treatment standard for those high-risk patients who failed standard treatment," remarked Professor Dr. med. Frederik Marmé, MD, PhD, Section Lead for Gynecological Oncology, University Medical Center, Mannheim, Germany, and designated Principal Investigator of the SASCIA trial.

BLA Resubmission Timeline Update

Based on the remaining activities for compilation of the BLA, and preparations for a pre-approval inspection, the Company revised its re-submission guidance from early fourth quarter to the late November or early December timeframe.

Reference

Untch M, Jackisch C, et al. Nab-Paclitaxel Improves Disease Free Survival in Early Breast Cancer: GBG 69-GeparSepto. J Clin Oncol. 2019 September 1;37:2226-2234.
About Sacituzumab Govitecan

Sacituzumab govitecan, Immunomedics’ most advanced product candidate, is a novel, first-in-class antibody-drug conjugate (ADC) delivering SN-38, a potent topoisomerase I inhibitor, directly to tumor cells by targeting the Trop-2 antigen expressed by many solid cancers. Based on encouraging Phase 1/2 results, the U.S. Food and Drug Administration has granted sacituzumab govitecan Breakthrough Therapy Designation for the treatment of patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease.

On September 28, 2019 ESSA Pharma Inc. (Nasdaq: EPIX) (TSXV: EPI), a pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported new preclinical data on ESSA’s lead Investigational New Drug ("IND") candidate at the 2019 American Urological Association ("AUA") Annual Meeting (Press release, ESSA, SEP 28, 2019, View Source [SID1234539899]).

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 an oral poster presentation titled, "EPI-7386 is a novel N-terminal domain androgen receptor inhibitor for the treatment of prostate cancer", a deeper preclinical characterization of EPI-7386 was presented. The poster shows that, in preclinical studies, EPI-7386 demonstrates:

Activity in multiple in vitro full length androgen receptor (AR) and AR-V7 splice variant driven cellular models.
Robust antitumor activity as a single agent and in combination with enzalutamide in the VCaP xenograft prostate cancer model.
Antitumor activity in enzalutamide-resistant prostate cancer xenograft models, 22Rv1 and LNCaP95, with no antitumor activity, as expected, in a non-functional androgen receptor PC-3 prostate cancer xenograft model.
Wide therapeutic index as demonstrated by a broad dose response in the VCaP model.
High plasma exposures in animal studies using a new suspension formulation.
Abstract ID:

503P

Abstract Title:

EPI-7386 is a novel N-terminal domain androgen receptor inhibitor for
the treatment of prostate cancer

Presenter:

Ronan Le Moigne, PhD

Date:

Saturday September 28, 2019

Time:

12:00pm CEST

Location:

Hall 4, Fira Gran Via, Barcelona, Spain

On September 28, 2019 Zymeworks Inc. (NYSE/TSX: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, reported updated data from the ongoing multi-center Phase 1 clinical trial evaluating ZW25 in patients with HER2‑expressing solid tumors, including biliary tract cancer (BTC), colorectal cancer (CRC), gynecological cancers, and gastroesophageal adenocarcinoma (GEA), in a poster discussion presentation at the ESMO (Free ESMO Whitepaper) 2019 Congress, taking place September 27 – October 1 in Barcelona, Spain (Press release, Zymeworks, SEP 28, 2019, View Source [SID1234539892]).

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 data presented today at ESMO (Free ESMO Whitepaper) confirm previous findings that ZW25 monotherapy can provide durable disease control in patients with a variety of HER2-expressing solid tumors that have progressed following standard of care therapies, including HER2-targeted agents," said Diana Hausman, M.D., Chief Medical Officer at Zymeworks. "Notably, the single agent objective response rate in biliary tract cancer is highly encouraging given the poor prognosis and limited treatment options for these patients. We are working closely with regulatory agencies to initiate a registration-enabling Phase 2 trial in second-line HER2‑expressing biliary tract cancer with the goal of bringing ZW25 to patients as quickly as possible."

Based on the data from the ongoing Phase 1 study, Zymeworks has initiated a broad clinical development program for ZW25 in multiple HER2-expressing cancers. In addition to the Phase 2 BTC trial announced today, Zymeworks is continuing to evaluate ZW25 as a potential treatment for patients with other HER2-expressing cancers, including CRC and gynecological cancers (Phase 1; NCT02892123). For patients with HER2-expressing GEA, ZW25 is being developed as a first-line treatment in combination with standard of care chemotherapy (Phase 2; NCT03929666). Zymeworks also plans to initiate a Phase 2 study of ZW25 in combination with a CDK4/6 inhibitor and hormone therapy in third-line HER2-expressing, HR-positive breast cancer.

ZW25 Clinical Results Presented Today
The Safety, Efficacy and Biomarker Results of the HER2-Targeted Bispecific Antibody ZW25 in HER2-Expressing Solid Tumors (Abstract# 3575, Poster Discussion on Saturday, September 28 at 4:30 pm CEST)

Findings from this ongoing Phase 1 study of ZW25 in patients with HER2-expressing solid tumors were last presented at the 2018 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium. The updated results were presented today by Dr. Funda Meric-Bernstram, M.D., Clinical Investigator and Chair of the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center.

Data were reported from 58 patients diagnosed with HER2-expressing solid tumors other than breast cancer who received ZW25 at the recommended dose of either 10 mg/kg weekly or 20 mg/kg every other week. Patients had a median age of 61 years and received a median of four prior therapies. Thirty-two (55%) patients received prior HER2‑targeted therapies including 87% of GEA patients. Of all patients, 23 were diagnosed with GEA, 13 with CRC, nine with BTC, and 13 with other HER2‑expressing cancers, including endometrial, ovarian, pancreatic, and salivary gland.

At the time of data cut-off, 46 of 58 patients were response evaluable. Overall, the majority of patients experienced a decrease in their target lesions with a disease control rate of 72%, comprising 16 (35%) patients with partial responses and 17 (37%) with stable disease. The objective response rate in the six evaluable biliary tract cancer patients was 67%, with the majority of patients experiencing disease control greater than six months. In the 11 CRC and 19 GEA patients, the objective response rates were 36% and 32%, respectively. The overall median progression-free survival was 5.2 months, with 27 (47%) of the 58 total patients still on study at the time of data cut-off.

Among all patients, ZW25 was well tolerated as an outpatient therapy. The most common adverse events were diarrhea, infusion-related reaction, and nausea. All treatment-related adverse events occurring in 10% or more of patients were Grade 1 or 2.

About the Phase 1 Clinical Trial

Zymeworks’ Phase 1 study has three parts. From part one of the study (the dose-escalation phase), the recommended single-agent dose was determined to be 20 mg/kg once every two weeks or 10 mg/kg weekly. In the second part of the study (the cohort expansion phase), additional patients are being enrolled to further assess ZW25’s single-agent tolerability and anti-tumor activity against a variety of cancer types in different settings. The third part of the study (the combination phase) is underway and evaluating ZW25 in combination with selected chemotherapy agents in gastroesophageal and breast cancer patients with HER2 high or lower HER2 expression levels.

About ZW25

ZW25 is being evaluated in Phase 1 and Phase 2 clinical trials across North America and South Korea. It is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging anti-tumor activity in patients. Zymeworks is developing ZW25 as a HER2-targeted treatment option for patients with any solid tumor that expresses HER2. The FDA has granted Fast Track designation to ZW25 for first-line gastroesophageal adenocarcinoma in combination with standard of care chemotherapy and Orphan Drug designation to ZW25 for the treatment of both gastric and ovarian cancers.

On September 28, 2019 Forbius, a clinical-stage protein engineering company that develops biotherapeutics to treat fibrosis and cancer, reported results from its non-clinical GLP toxicology program with first-in-class selective TGF-beta inhibitor AVID200 and evidence of TGF-beta target engagement in patients treated with this novel immuno-oncology agent at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Annual Congress in Barcelona (Press release, Forbius, SEP 28, 2019, View Source [SID1234539891]).

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 presentation detailed for the first time that AVID200 administered at doses of ≥1 mg/kg sequestered its target TGF-beta in patient blood over the entire dosing period.

Key highlights of today’s presentation at ESMO (Free ESMO Whitepaper) (#504P):

AVID200 selectively neutralizes TGF-beta 1 & 3 with pM potency in vitro, and increases T-cell-mediated cytotoxicity as well as immune checkpoint inhibitor efficacy in syngeneic mouse tumor models
AVID200 was well tolerated in 1- and 6-month GLP toxicology studies in non-human primates
AVID200 in patient blood sequestered peripheral TGF-beta over the entire dosing period
A Phase 1a AVID200 monotherapy dose-escalation clinical trial is currently enrolling solid tumor patients (AVID200-03; NCT03834662)
About TGF-beta 1 & 3

TGF-beta 1 & 3 are the main oncogenic TGF-beta isoforms expressed by many solid tumors. They are believed to play a major role in T-cell suppression, fibrosis, and resistance to anti-PD-(L)1 therapies such as nivolumab (Opdivo) and pembrolizumab (Keytruda) (Chakravarthy et al., Nature Comm., 2018; Tauriello et al., Nature, 2018; Mariathasan et al., Nature, 2018).

About AVID200 and the AVID200-03 Trial (NCT03834662)

AVID200 is an isoform-selective and highly potent inhibitor of TGF-beta 1 & 3 undergoing Phase 1 clinical testing in solid tumors and fibrotic diseases. TGF-beta 1 & 3 are the principal disease-driving isoforms, while TGF-beta 2 is responsible for normal cardiac function and hematopoiesis.

AVID200’s selectivity for TGF-beta 1 & 3 was designed to achieve optimal efficacy while circumventing cardiac and other safety issues that have limited the applicability of older-generation, non-selective TGF-beta inhibitors. Therefore, AVID200 is positioned to be an effective and well-tolerated therapeutic in a variety of clinical settings, including in combination with anti-PD-(L)1 therapy.

AVID200-03 (NCT03834662) is an open label, multicenter, dose-escalation study to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor effects of AVID200 in patients with advanced or metastatic solid tumor malignancies.