On December 10, 2021 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) a clinical-stage biotechnology company developing eganelisib, a first-in-class, oral, immuno-oncology macrophage reprogramming therapeutic, reported updated data from the ongoing MARIO-3 clinical study during the 2021 San Antonio Breast Cancer Symposium (SABCS). MARIO-3 is the Company’s ongoing Phase 2 study evaluating eganelisib in combination with atezolizumab (Tecentriq) and nab-paclitaxel (Abraxane) in frontline metastatic triple negative breast cancer (TNBC) (Press release, Infinity Pharmaceuticals, DEC 10, 2021, View Source [SID1234596757]).

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"These promising updated data suggest that the addition of eganelisib to atezolizumab and nab-paclitaxel has the potential to provide improved patient outcomes over benchmark IMpassion130 data in front-line metastatic TNBC," said Hatem Soliman, M.D., MARIO-3 Investigator and Medical Director, Clinical Trials Office at the Moffitt Cancer Center. "Tumor reductions in 88.6% of evaluable patients were associated with a disease control rate of 81.4% in patients with PD-L1 negative tumors who are among the most challenging to treat. Importantly, we see that this impressive disease control rate is translating into durable clinical benefit, regardless of PD-L1 status, with encouraging mPFS compared to the IMpassion130 benchmark study. These compelling findings, combined with eganelisib’s safety and tolerability profile, indicate that eganelisib has the potential to become an important new treatment option for advanced TNBC patients."

Adelene Perkins, Chief Executive Officer and Chair, Infinity Pharmaceuticals, said, "With a median duration of follow-up of almost 10 months, the durable clinical benefit seen with the eganelisib combination reinforces our vision of bringing better therapies to frontline TNBC patients. When compared to the IMpassion130 benchmark data, a 47% improvement in median PFS for patients with PD-L1 positive tumors and a 30% improvement in median PFS for patients with PD-L1 negative tumors provides consistent and compelling evidence of eganelisib’s potential to improve outcomes for these patients."

MARIO-3 Key Data Updates:

This data update includes 50 patients enrolled and 44 evaluable as of the October 2, 2021 data cutoff date, with a median duration of follow up of 9.9 months.
Of evaluable patients, tumor reduction was observed in 92.8% of patients with PD-L1 positive tumors (13/14) and 85.2% of patients with PD-L1 negative tumors (22/27).
Disease control rate (DCR)
92.8% (13/14) DCR in patients with PD-L1 positive tumors: CR 14.3% (2/14), PR 57.1% (8/14), SD 21.4% (3/14)
81.4% (22/27) DCR in patients with PD-L1 negative tumors: complete response (CR) 0% (0/27), partial response (PR) 48.1% (13/27), stable disease (SD) 33.3% (9/27)
Progression free survival (PFS)
In patients with PD-L1(+) tumors, median PFS in MARIO-3 was 11.0 months, a 47% improvement in mPFS compared to the 7.5 months reported for atezolizumab and nab-paclitaxel alone in IMpassion130
In patients with PD-L1(-) tumors, median PFS in MARIO-3 was 7.3 months, a 30% improvement compared to the 5.6 months reported for atezolizumab and nab-paclitaxel alone in IMpassion130
72% of the 32 PD-L1 (+) and PD-L1(-) patients treated since the June 26, 2021 data cut remain on treatment
67% of the PD-L1(-) patients who reached the median PFS of 7.3 months remain on treatment
Safety
MARIO-3 did not demonstrate any new safety signals compared to benchmark trials, and its safety profile was consistent with expectations for the three component drugs. The most common Grade 3 or higher treatment-related TEAEs were hepatic AEs (18%); neutropenia AEs (16%); skin AEs (12%); fatigue, diarrhea and peripheral sensory neuropathy (6% each); and vomiting and weight decreased (2% each). Seven patients (14%) discontinued treatment for treatment-related TEAEs and nine patients (18%) had treatment-related SAEs.
Quantification across 11 paired tumor biopsies shows increased immune activation and decreased immune suppression including an increase in CD8+ T cells, activated T cells, and anti-tumor M1 macrophages and a decrease in tumor cells and pro-tumor M2 macrophages resulting in an increase in the M1:M2 ratio.
Paired tumor biopsy data show 5 of 8 patients with PD-L1(-) tumors converting to PD-L1(+) two months after treatment utilizing the same 1% PD-L1 cutoff standard used in the benchmark IMpassion130 study. PD-L1 expression also increased in the three patients with PD-L1(+) tumors who started the study above the 1% cutoff. None of the patients converting to PD-L1(+) or patients with PD-L1(+) tumors who experienced increased PD-L1 expression had disease progression.
KOL Event Information

Infinity will host a KOL event today, December 10, 2021, at 9:30AM ET with Hatem Soliman, M.D., MARIO-3 Investigator and Medical Director, Clinical Trials Office at the Moffitt Cancer Center, to review the MARIO-3 data presented at SABCS.

To register for the webinar, please click here.

On December 10, 2021 Johnson & Johnson (NYSE: JNJ) reported thatit will host a conference call for investors at 8:30 a.m. (Eastern Time) on Tuesday, January 25th to review fourth-quarter results. Joaquin Duato, incoming Chief Executive Officer, Joseph J. Wolk, Executive Vice President and Chief Financial Officer and Jessica Moore, Vice President, Investor Relations will host the call (Press release, Johnson & Johnson, DEC 10, 2021, View Source;johnson-to-host-investor-conference-call-on-fourth-quarter-results-301442424.html [SID1234596778]).

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Investors and other interested parties can access the webcast/conference call in the following ways:

The webcast and presentation material are accessible at Johnson & Johnson’s website www.investor.jnj.com. A replay of the webcast will be available approximately three hours after the conference call concludes.
By telephone: for both "listen-only" participants and those financial analysts who wish to take part in the question-and-answer portion of the call, the telephone dial-in number in the U.S. is 877-869-3847. For participants outside the U.S., the dial-in number is 201-689-8261.
A replay of the conference call will be available until approximately 12:00 a.m. on February 8th. The replay dial-in number for U.S. participants is 877-660-6853. For participants outside the U.S., the replay dial-in number is 201-612-7415. The replay conference ID number for all callers is 13725514.
The press release will be available at approximately 6:45 a.m. (Eastern Time) the morning of the conference call.
Please refer to www.investor.jnj.com for a complete list of currently planned earnings webcast/conference calls. Please note the first-quarter date of Tuesday, April 19th, 2022.

On December 10, 2021 Intensity Therapeutics, Inc. ("Intensity"), a clinical-stage biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported safety, pharmacokinetic, biomarker and efficacy data using INT230-6, with and without pembrolizumab, in heavily pretreated refractory breast cancer patients as part of the Company’s phase 1/2 study, IT-01 (Press release, Intensity Therapeutics, DEC 10, 2021, View Source [SID1234596779]). The presentation was made at the San Antonio Breast Cancer Symposium (SABCS), being held virtually and in-person at the Henry B. Gonzales Convention Center in San Antonio, Texas.

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The seven heavily pre-treated breast cancer subjects were enrolled in the study after having progressed on a median of six (range 2 to 10) prior therapies. The INT230-6 monotherapy subjects (n=4) were more heavily pre-treated with a median of eight prior therapies vs. three prior therapies for pembrolizumab combination subjects (n=3). The disease control rate (DCR), defined as the percent of breast cancer subjects with a complete response, partial response, or stable disease at the first radiologic assessment, was 57%. Study authors reported a median overall survival (mOS) of 12 months (CI:7.2, NR), which compares favorably to results seen in phase 1 studies of subjects with highly refractory or triple negative breast cancer. Abscopal effects were seen in a non-injected visceral lesion in 1 of 4 INT230-6 monotherapy subjects. A number of patients came off study after completion of INT230-6 dosing without disease progression. One subject continued receiving INT230-6 injections despite a new lesion.

Peak plasma concentrations of the agent vinblastine were less than five percent (5%) of that predicted, based on historical IV kinetics, indicating that 95% of the drug remains in the tumor. Treatment related adverse events (TRAEs) were favorable with or without pembrolizumab. Only one subject experienced a grade 3 TRAE (monotherapy group) and there were no grade 4 or grade 5 TRAEs. Tissue analysis of matched paired (pre- and 28 days post-dose) biopsies in injected tumors from subjects receiving their first INT230-6 treatment cycle (two doses, n=3) had an average reduction in viable cancer cells of sixty-nine percent (69%). Immunohistochemistry results showed influx of CD4 and CD8 T-cells into the tumor microenvironment.

"Preliminary data suggests that INT230-6 demonstrates direct tumor killing in metastatic breast cancer subjects including those with triple negative breast cancer (TNBC) and may elicit an anti-cancer immune response within the injected tumor with or without pembrolizumab," stated poster presenter and study investigator, Philippe Bedard, M.D., Clinician Investigator, Princess Margaret Cancer Centre in Toronto Canada. "Additionally, INT230-6 treatment related adverse events are mostly low grade and the drug is well-tolerated either as a monotherapy or in combination with anti-PD-1 therapy, pembrolizumab. These results provide evidence to continue studying this novel therapeutic drug approach in breast cancer."

"The data presented at the San Antonio Breast Cancer Symposium using INT230-6 alone or in combination with pembrolizumab were generated from refractory breast cancer patients treated in the dose escalation portion of our phase 1 clinical study, IT-01, and these results are encouraging. We have also learned a great deal about our drug in breast cancer from our trial in metastatic patients and our phase 2 randomized INVINCIBLE study, which is testing INT230-6 in breast cancer patients in a presurgical setting," said Lewis H. Bender, President and Chief Executive Officer of Intensity Therapeutics. "We are excited about conducting additional clinical studies using INT230-6 in metastatic breast cancer as part of INT230-6’s Fast Track designation as well as in presurgical patients, as there remains an unmet medical need for safer more effective treatments in both settings."

Presentation Title: Safety and efficacy of INT230-6, a potential first-in-class intratumoral therapy, in monotherapy and in combination with pembrolizumab: Results from the IT-01 study [KEYNOTE-A10] in subjects with locally advanced, unresectable and metastatic breast cancer
Abstract: 541
Poster Number: P-5-16-13
First Author: Philippe Bedard, MD, FRCPC, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Full Authors Block: Philippe Bedard1, Lillian L Siu1, Jacob Thomas2, Diana Hanna3, Anthony J Olszanski4, Nilofer Azad5, Giles Whalen6, Matthew Ingham7, Syed Mahmood8, Lewis H Bender8, Ian B Walters8 and Anthony El-Khoueiry2. 1Princess Margaret Cancer Centre, Toronto, ON, Canada2USC Norris Comprehensive Cancer Center, Los Angeles, CA;3USC Hoag Memorial Hospital Presbyterian, Newport Beach, CA;4Fox Chase Cancer Center, Philadelphia, PA;5Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD;6UMass Memorial Medical Center – University Campus, Worcester, MA;7New York Presbyterian Hospital/Columbia University Medical Center, New York, NY;8Intensity Therapeutics, Inc., Westport, CT,
Session: Treatment: Therapeutic Strategies – New Drugs and Treatment Strategies
Date: Friday, December 10, 2021
Time: 7:00AM – 8:30AM Central Standard Time

The presentation will be accessible on the "Publications, Papers and Posters" section of Intensity’s website at: View Source on December 10, 2021.

About INT230-6

INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug is composed of two proven, potent anti-cancer agents, cisplatin and vinblastine, and an amphiphilic penetration enhancer molecule that helps disperse the drugs throughout tumors for diffusion into cancer cells. In addition to local disease control, direct killing of the tumor by INT230-6 releases neoantigens specific to the patient’s malignancy, leading to engagement of the immune system and systemic anti-tumor effects. Importantly, these effects are mediated without the immunosuppression of concomitant systemic chemotherapy.

INT230-6 is currently being evaluated in several phase 2 cohorts (NCT03058289) in patients with various advanced solid tumors as part of Study IT-01. In 2019, the Company signed a clinical collaboration agreement with Merck Sharpe & Dohme (Merck) to evaluate the combination of INT230-6 and KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 (programmed death receptor-1) therapy, in patients with advanced pancreatic, colon, squamous cell and bile duct malignancies. In 2020, the Company executed a clinical collaboration agreement with Bristol-Myers Squibb Company to evaluate the combination of INT230-6 with Bristol-Myers Squibb’s anti-CTLA-4 antibody, Yervoy (ipilimumab), in patients with advanced liver, breast and sarcoma cancers. In 2021, the Company executed agreements with the Ottawa Hospital Research Institute and the Ontario Institute of Cancer Research to study INT230-6 in a randomized controlled neoadjuvant phase 2 study in women with early stage breast cancer (the INVINCIBLE study) (NCT04781725).

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

On December 9, 2021 Totus Medicines, a drug discovery company using breakthrough chemical biology to make the entire human genome druggable, reported its revolutionary drug program targeting PI3Kα, the most commonly mutated cancer oncogene (Press release, Totus Medicines, DEC 9, 2021, View Source [SID1234596658]). The company also announced a $40 million Series A funding round led by investors DCVC Bio and Northpond Ventures and supported by Camford Capital with original seed funding from Social Impact Capital. The Series A financing will be used to expand and scale Totus Medicines’ proprietary drug discovery platform and advance the company’s lead program into the clinic.

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Totus Medicines’ TOS-358 drug program targets the PI3Kα mutation, which impacts more than 500,000 people in the U.S. every year and drives a significant percentage of breast, colon, lung, bladder, stomach, and other cancers. The pharmaceutical industry has spent decades and billions of dollars attempting to target PI3Kα, and current inhibitors only achieve moderate success in <10% of patients with PI3Kα-mutant cancers.

In just 18 months, Totus has used its proprietary drug discovery platform to develop TOS-358, which shows strong preclinical efficacy across PI3Kα-mutant tumor types where current PI3Kα inhibitors show weak to no efficacy. In patient-derived mouse xenograft models, TOS-358 induces tumor regressions across breast, colon, lung, stomach, and other models, while current inhibitors show mild effects. Totus Medicines will begin clinical trials for the TOS-358 drug program in the second half of 2022.

"Our drug discovery platform is capable of creating treatments for previously untreatable diseases," said Neil Dhawan, Ph.D., co-founder and CEO of Totus Medicines. "We are drugging undruggable targets at scale, moving us closer to a world where every physician and every patient can look forward to effective treatments for the most devastating illnesses. The TOS-358 drug program is a crowning achievement in that mission, and we look forward to advancing the program—and many others—into the clinic."

Totus Medicines’ platform uses proprietary molecular tags that track drug binding in individual cells to screen billions of drug molecules across thousands of genes in parallel. By combining this approach with breakthrough machine learning techniques, the company has developed the next generation of cellular analysis. Continuously learning and adapting, the Totus platform is more effective, less costly, and thousands of times faster than legacy drug discovery methods, enabling the rapid translation of therapies to patients. Totus aims to screen two billion compounds across the human genome within the next two years to unlock precise, effective drugs across hundreds of high-value drug targets.

"The Series A financing will allow us to refine and grow the Totus platform to find new treatments for previously untreatable diseases—faster and more successfully than has ever been possible," said Jason Pontin, a Partner at DCVC, and a board member and co-founder of Totus Medicines. "The promise of Totus Medicines is that doctors can offer life-changing medicines to patients who would otherwise have little hope."

On December 9, 2021 Sapience Therapeutics, Inc., a biotechnology company focused on the discovery and development of peptide therapeutics to address difficult-to-treat cancers, reported that it will present multiple posters on its lead program, ST101, at the 2021 San Antonio Breast Cancer Symposium, being held in San Antonio, Texas in a hybrid format (in-person and virtual), December 7-10, 2021 (Press release, Sapience Therapeutics, DEC 9, 2021, View Source [SID1234596689]).

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Presentation details for the posters are as follows:

Presentation Title: Phase 1 study of ST101, a first-in-class peptide antagonist of CCAAT/-binding protein β (C/EBPβ), in patients with advanced solid tumors, with a phase 2 expansion in patients with hormone receptor positive breast cancer (HR+ BC)
Date/Time: Thursday, December 9, 2021 5:00 PM-6:30 PM CT

Presentation Title: C/EBPβ antagonist peptide, ST101, as a novel therapeutic for breast cancer
Date/Time: Friday, December 10, 2021 7:00 AM-8:30 AM CT

About ST101
ST101, a peptide antagonist of C/EBPβ, is currently being evaluated in an ongoing Phase 1-2 clinical study in patients with advanced unresectable and metastatic solid tumors (NCT04478279). In the ongoing study, ST101 has demonstrated clinical proof-of-concept with a RECIST 1.1-confirmed partial response (PR) in a patient with cutaneous melanoma and evidence of long-lasting stable disease in several additional patients. Following conclusion of the final dose-escalation cohort, Sapience plans to initiate four Phase 2 expansion cohorts in refractory, locally advanced and metastatic cutaneous melanoma, hormone-receptor-positive breast cancer, castrate-resistant prostate cancer, and glioblastoma starting in the second half of 2021. ST101 has been granted orphan drug product designation from the U.S. Food and Drug Administration and orphan medicinal product designation for the treatment of glioma by the European Commission.