On September 8, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage oncology company, developing new precision medicine treatment options for cancer patients in indications with the greatest unmet medical need including KRAS-mutated colorectal cancer, pancreatic cancer, and castrate-resistant prostate cancer, reported new data from its lead clinical program evaluating onvansertib in combination with standard-of-care (SOC) FOLFIRI/bevacizumab for second-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC) (Press release, Cardiff Oncology, SEP 8, 2021, View Source [SID1234587440]).

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"Our Phase 1b/2 trial continues to generate data suggesting that the addition of onvansertib to SOC results in an objective response rate and median progression-free survival that substantially exceed those previously achieved with SOC alone," said Katherine L. Ruffner, M.D., chief medical officer of Cardiff Oncology. "Radiographic responses have been observed across multiple KRAS mutation variants, which speaks to a key advantage of onvansertib over competing agents targeting individual mutations. These impressive results, which have remained consistent across both academic and community trial sites, highlight the potential for onvansertib to address the unmet need for new second-line therapeutic options to treat patients with KRAS-mutated mCRC. I look forward to the trial’s continued advancement and future data readouts."

Highlights from today’s data announcement include:

Efficacy data in patients evaluable for disease response as of data cutoff date (July 2, 2021):

Patients treated per protocol at the recommended Phase 2 dose (RP2D; 15 mg/m2) across both Phase 1b and Phase 2:
8 of 19 (42%) achieved an initial partial response (PR) as of the data cutoff date
7 of 19 (37%) have achieved a confirmed PR (based on further follow-up of patients with an initial PR as of data cutoff date)
Objective response rates observed in historical control trials in similar patient populations treated with standard of care are 5-13%1-4

Patients evaluable for response treated at all dose levels (12 mg/m2, 15 mg/m2, 18 mg/m2) across both phases of the study
12 of 32 (38%) achieved an initial PR as of the data cutoff date
10 of 32 (31%) have achieved a confirmed PR (based on further follow-up of patients with an initial PR as of data cutoff date)
Median progression free survival (mPFS)

mPFS has not yet been reached in patients treated per protocol at the RP2D
mPFS across all response-evaluable patients (n = 32) is 9.4 months (95% confidence interval: 7.8 – not yet reached)
mPFS of ~4.5-5.7 months has been reported in trials used as historical controls1-4
Biomarker data as of data cutoff date across all patients:

Partial responses (PRs) were observed across different KRAS mutation variants, including the 3 most common observed in colorectal cancer (G12D, G12V, G13D)
Patients achieving a best response of PR showed the greatest decreases in plasma KRAS mutant allelic frequency (MAF) after 1 cycle (28 days) of therapy
Safety data as of data cutoff date across all patients:

The combination of onvansertib and FOLFIRI/bevacizumab was shown to be well-tolerated with only 10% (49/490) of reported treatment-emergent adverse events (TEAEs) being G3/G4
Most reported treatment-related adverse events (TRAEs) were manageable and reversible with supportive care
Mark Erlander, Ph.D., chief executive officer of Cardiff Oncology, commented, "The strong signal of efficacy and favorable tolerability profile observed in this trial bodes well not only for our lead mCRC program, but for each of our KRAS-focused clinical programs. The meaningful improvements we are seeing in treatment response relative to historical controls demonstrate the value of combination therapy and support the synergistic effect observed preclinically when onvansertib is added to standard-of-care irinotecan and 5-FU (FOLFIRI). We are also seeing compelling biomarker results that highlight the potential utility of plasma KRAS MAF as a predictive tool that could aid in the design of subsequent trials. Looking forward, we anticipate the ongoing Phase 2 portion of the trial to provide additional data catalysts that will advance the clinical development of onvansertib, generate value for shareholders and, most importantly, provide new treatment options for patients."

Key Opinion Leader Webinar
The newly announced data are being discussed today at 4:00 PM ET as part of a key opinion leader (KOL) webinar being hosted by Cardiff Oncology. The webinar is featuring the clinical trial principal investigator, Heinz-Josef Lenz, M.D., FACP, USC Norris Comprehensive Cancer Center, key clinical advisor Afsaneh Barzi, M.D., Ph.D., City of Hope Comprehensive Cancer Center, and members of the Cardiff Oncology management team.

To attend the webinar, click here. A replay of the webinar will be available by visiting the "Events" section of the Cardiff Oncology website shortly after its conclusion.

About the Phase 1b/2 Trial of Onvansertib in KRAS-mutated mCRC
This is a multi-center, single-arm, Phase 1b/2 trial of onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab) to evaluate the safety and preliminary efficacy of the combination regimen in the second-line treatment of patients with KRAS-mutated mCRC. The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second–Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation, is enrolling patients with histologically confirmed metastatic and unresectable colorectal carcinoma harboring a KRAS mutation. Patients must also have failed treatment with, or be intolerant to, FOLFOX (fluoropyrimidine and oxaliplatin) with or without bevacizumab to be eligible. The trial is being conducted at the following cancer centers across the U.S.: USC Norris Comprehensive Cancer Center, The Mayo Clinic (Arizona, Rochester, and Jacksonville), Kansas University Medical Center (KUMC), CARTI Cancer Center and Inova Schar Cancer Institute. For more information on the trial, please visit View Source

References

Giessen et al., Acta Oncologica 2015, 54: 187-193
Cremolini et al., Lancet Oncol 2020, 21: 497–507
Antoniotti et al., Correspondence Lancet Oncol June 2020
Bennouna et al., Lancet Oncol 2013; 14: 29–37

On September 8, 2021 NETRIS Pharma reported that a "trial in progress" abstract has been accepted to the ESMO (Free ESMO Whitepaper) congress (European Society for Medical Oncology) taking place September 16th-20th (Press release, Netris Pharma, SEP 8, 2021, View Source [SID1234587455]).

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The corresponding e-Poster "GYNET – Safety & efficacy of NP137 in combination with chemotherapy and/or Pembrolizumab in patients with pretreated locally advanced/metastatic endometrial carcinoma or cervix carcinoma: an adaptative multi-arms randomized Phase I/II" will be presented by Prof. Isabelle Ray-Coquard as Principal Investigator.

On September 8, 2021 A-Alpha Bio, a biotechnology company that works with pharmaceutical industry partners to accelerate drug discovery with massively multiplexed measurements of protein interactions, reported that it has closed a $20M Series A Financing Round to dramatically expand capabilities and throughput (Press release, A-Alpha Bio, SEP 8, 2021, View Source [SID1234636941]). The round was led by Madrona Venture Group with participation from Perceptive Advisors’ Perceptive Xontogeny Venture Fund (PXV Fund) and Lux Capital. Madrona Venture Group’s Matt McIlwain and Xontogeny’s Ben Askew, Ph.D. have joined A-Alpha Bio’s Board of Directors as part of the financing.

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A-Alpha Bio is building a high-resolution model of biology by measuring millions of protein-protein interactions, leveraging the intersection of synthetic biology, protein engineering, and machine learning. Compared to traditional technologies for screening protein interactions, including biophysical and display platforms, A-Alpha Bio’s proprietary AlphaSeq platform is able to measure protein interactions at a scale and to a degree of precision that is otherwise inaccessible. The quantity and quality of AlphaSeq data is ideal for drug discovery and also critical for training highly predictive ML-models for protein-protein binding.

"Understanding and characterizing protein-protein interactions is fundamental to the future of drug discovery and development and we are excited to back this impressive team that is at the intersection of innovation – bringing together life and computer sciences to uncover previously inaccessible discoveries," said Matt McIlwain, Managing Director, Madrona Ventures Group. "We have been impressed by the traction David and the team have made since we invested in the seed round and believe they are well on their way to helping to develop treatments for diseases and create a data advantage that could change the future of antibody and small molecule discovery."

A-Alpha Bio will deploy the new capital announced today to build a new production laboratory, generate the largest ever database of protein interaction measurements, and fill key roles in their rapidly growing team. These investments will enhance the company’s partnerships with leading pharmaceutical companies to discover new drugs – with a focus on antibodies and molecular glues. With a massive and ever-growing protein interaction data asset, A-Alpha Bio also plans to expand their machine-learning capabilities to uncover the complex rules of protein binding and enable in silico modeling of complex protein interaction networks.

"Our mission is to improve human health by accelerating drug discovery with synthetic biology and machine learning. I’m incredibly proud of the phenomenal team we’ve built and the impactful work we’ve already accomplished with leading pharma and biotech partners," said Dr. David Younger, Co-Founder and CEO of A-Alpha Bio. "Our Series A investors share our vision and optimism for the future of medicine. I’m especially delighted to welcome Matt McIlwain and Ben Askew as Board Members who bring decades of experience building high-impact companies across the technology and pharmaceutical industries."

Protein interactions are central to antibody and small-molecule drugs, and AlphaSeq represents the first high-throughput and quantitative approach for measuring protein-protein binding. By leveraging AlphaSeq, partners have been able to accelerate antibody discovery by measuring millions of interactions between antibodies and antigens for high-throughput determination of properties like affinity, specificity, cross-reactivity, and epitope. Instead of narrowly funnelling an antibody library and characterizing the few strongest binders, AlphaSeq allows partners to maintain a wide funnel with thousands of antibodies to avoid missing therapeutic candidates with unique and desirable properties. AlphaSeq is also leveraged for molecular glue target discovery by measuring weak and likely druggable interactions between a library of E3 ubiquitin ligases and a library of neo-substrates.

"When it comes to measuring protein-protein interactions and assisting pharma in the discovery of antibodies and molecular-glue targets, AlphaSeq is unmatched," said Ben Askew Ph.D., Partner, PXV Fund. "AlphaSeq is enabling pharma companies to find the high-value needles in the haystack, a process so prohibitively expensive, rare, or slow that these opportunities might have never been found. We’re thrilled to support A-Alpha Bio’s next phase of growth as they continue to set new standards for protein and molecular glue research."

To date, A-Alpha Bio has worked with a number of partners across the pharmaceutical and biotech industry to advance drug discovery, ranging from mid-sized biotechs to top-ten pharma. Additionally, A-Alpha Bio has ongoing awards from the Bill & Melinda Gates Foundation to support the discovery of therapeutics for infectious diseases and the National Science Foundation to support molecular-glue target discovery and ML-guided antibody discovery.

On September 8, 2021 Bolt Biotherapeutics, Inc. (Nasdaq: BOLT), a clinical-stage biotechnology company pioneering a new class of immuno-oncology agents that combine the targeting precision of antibodies with the power of both the innate and adaptive immune systems, reported that it has entered into a clinical collaboration and supply agreement with Bristol Myers Squibb (NYSE: BMY) to investigate Bolt Biotherapeutics’ BDC-1001 in combination with Bristol Myers Squibb’s PD-1 checkpoint inhibitor Opdivo (nivolumab) (Press release, Bolt Biotherapeutics, SEP 8, 2021, View Source [SID1234618695]). BDC-1001 is a HER2-targeting Boltbody immune-stimulating antibody conjugate (ISAC) in development for the treatment of patients with HER2-expressing solid tumors .

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"We look forward to working with BMS in our continued development of BDC-1001, which has shown promising results in preclinical and early clinical studies," said Randall Schatzman, CEO of Bolt Biotherapeutics. "Our unique ISAC approach initiates an innate and an adaptive immune response that may be synergistic with BMS’ innovative PD-1 inhibitor Opdivo. The combination of BDC-1001 and Opdivo holds potential as a treatment for cancer patients, and we welcome the opportunity to investigate this in a clinical setting." He added, "We remain grateful to all of the healthcare professionals, scientists, patients, and families involved with Bolt’s clinical studies."

BDC-1001 is a human epidermal growth factor receptor 2 (HER2) ISAC comprised of a HER2-targeting biosimilar of trastuzumab conjugated to one of Bolt’s proprietary TLR7/8 agonists with an intervening non-cleavable linker, for the treatment of patients with HER2-expressing solid tumors. It is currently being investigated in a Phase 1/2 clinical trial (NCT04278144) in patients with solid tumors, including breast, gastroesophageal and colorectal, that are HER2+ or HER2-low, for which Bolt recently presented preliminary data detailing safety, tolerability, and signs of activity at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The trial is being conducted in four parts, with dose-escalation and dose-expansion parts exploring both monotherapy and combination with a PD-1 checkpoint inhibitor. BMS will provide Opdivo for the combination dose escalation and combination dose expansion portions of the trial. Bolt Biotherapeutics is the study sponsor and will be responsible for costs associated with the trial execution. The combination dose escalation is expected to start later in 2021.

Opdivo is a trademark of Bristol-Myers Squibb Company.

About the Boltbody Immune-Stimulating Antibody Conjugate (ISAC) Platform
ISACs are a new category of immunotherapy that combines the precision of antibody targeting with the strength of the innate and adaptive immune systems. Boltbody ISACs are comprised of three primary components: a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant to activate the patient’s innate immune system. By initially targeting a single marker on the surface of a patient’s tumor cells, an ISAC can create a new immune response by activating and recruiting myeloid cells. The activated myeloid cells start a feed-forward loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This reprograms the tumor microenvironment and invokes an adaptive immune response that targets the tumor, with the goal of durable responses for patients with cancer.

On September 8, 2021 Bristol Myers Squibb (NYSE:BMY) reported that it will announce results for the third quarter of 2021 on Wednesday, October 27, 2021 (Press release, Bristol-Myers Squibb, SEP 8, 2021, View Source [SID1234587367]). During a conference call at 8 a.m. ET on October 27, 2021, company executives will review financial results and address inquiries from investors and analysts.

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Investors and the general public are invited to listen to a live webcast of the call at View Source or by using this link which becomes active 15 minutes prior to the scheduled start time and entering your information to be connected. Investors and the general public can also access the live webcast by dialing in the U.S. toll free 800-263-0877 or international +1 313-209-7315, confirmation code: 8911662. Materials related to the call will be available at the same website prior to the conference call.

A replay of the call will be available on View Source or by dialing in the U.S. toll free 888-203-1112 or international +1 719-457-0820, confirmation code: 8911662. The replay will be available beginning at 11:30 a.m. ET on October 27 through 11:30 a.m. ET on November 10, 2021.