On June 5, 2021 Agendia, Inc., a world leader in precision oncology for breast cancer, reported that data from the landmark MINDACT study will be shared at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in an oral presentation (Press release, Agendia, JUN 5, 2021, View Source [SID1234583617]). The presentation will detail an additional risk threshold previously established within the MammaPrint Low Risk category, identifying patients with an Ultra Low Risk of distant recurrence, essentially meaning the patient’s tumor is very unlikely to recur or metastasize over at least 20 years of follow-up, according to prior studies. This information could be helpful in further tailoring adjuvant treatment for patients with early stage breast cancer.

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In the oral presentation, titled "Outcome of patients with an ultralow risk 70-gene signature in the MINDACT trial," Josephine Lopes Cardozo, MD, first author of the abstract, PhD Candidate at the Netherlands Cancer Institute and fellow at the EORTC, will outline that in the MINDACT study, patients with an UltraLow Risk signature have an excellent prognosis, with 8-year breast cancer specific survival above 99% regardless of clinical risk status, and an 8-year distant metastasis free interval of 97%. The presentation, part of ASCO (Free ASCO Whitepaper) 2021’s Breast Cancer track, can be accessed here.

"The Ultra Low threshold identifies patients who may be candidates for further de-escalation of treatment," said Dr. Lopes Cardozo. "To give the patient’s care team this kind of prognostic insight at the time of diagnosis will hopefully allow for many patients to avoid over treatment and further reduce the risk of side effects while maintaining excellent survival."

The MINDACT trial, an independent, phase III, prospective, randomized clinical trial sponsored by the European Organization for Research and Treatment of Cancer (EORTC), was conducted with the primary goal of determining whether Agendia’s 70-gene MammaPrint test could be used to de-escalate clinically high risk patients with early stage breast cancer from chemotherapy treatment. The study enrolled nearly 7,000 patients with newly-diagnosed breast cancer, and at median long-term follow-up of 8.7 years, 46% of clinically high risk patients with a MammaPrint Low Risk result could forgo chemotherapy without negatively affecting their outcomes. These data were recently published in The Lancet Oncology.

The current study to be presented at ASCO (Free ASCO Whitepaper) focuses on the clinical characteristics and outcomes of the 1,000 women with a MammaPrint Ultra Low risk status enrolled in MINDACT. Consistent with three prior studies presented since 2017, these data show a nearly 100% breast cancer specific survival at 8 years, with 5 years of anti-estrogen therapy, and excellent outcomes (97.8% DMFI) for the 157 Ultra Low Risk women who received no systemic therapy.

"The confirmation of the clinical importance and excellent prognosis of the MammaPrint Ultra Low Risk category provides further support for the inclusion of this information in the management of endocrine therapy, particularly for those women experiencing severe side effects, and struggling to remain on their prescribed treatment," said William Audeh, MD, Chief Medical Officer at Agendia. "We are extremely proud to have contributed to the EORTC’s MINDACT study, which has influenced the clinical treatment of patients and will inspire ongoing translational research that will contribute to the library of data we need to personalize the treatment of breast cancer."

Beyond answering the traditional adjuvant chemotherapy question, the MINDACT study continues to produce a wealth of insights with immediately meaningful clinical implications and access to an unprecedented full genome dataset for further research, resulting in widespread health system cost savings.

At ASCO (Free ASCO Whitepaper) 2021, Agendia also presented a larger suite of data from the company’s groundbreaking FLEX registry, a large-scale, prospective, observational breast cancer study using whole transcriptome sequencing, recruiting patients from various ethnicities, ages and genders representative of the total breast cancer population as part of an ongoing effort to increase representation of diverse populations and data in clinical trials.

On June 04, 2021 Auransa, Inc., an artificial intelligence (AI) company developing precision medicines in areas of unmet medical needs, and Polaris Quantum Biotech (POLARISqb), a quantum drug design company, reported a research collaboration addressing therapeutics for neglected diseases disproportionately affecting women (Press release, Auransa, JUN 4, 2021, View Source [SID1234635628]).

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The partnership seeks to discover treatments that may tackle many such diseases, and their complementary expertise promises to seek solutions that elude medical research. Auransa is an AI-driven biotech company, with a pipeline of novel compounds for various diseases. Auransa’s proprietary predictive computational platform, SMarTR Engine, uses computational approaches to tackle disease heterogeneity to predict targets and compounds, generating insights from molecular data. POLARISqb built the first drug discovery platform using quantum computing, making the process ten times faster. POLARISqb’s TachyonTM platform scans billions of molecules from a massive chemical space, finding novel molecular drugs.

"We are excited about collaborating with Polaris to undertake a neglected area in the pharmaceutical industry. As women CEOs, we’ve joined forces to tackle female diseases like endometriosis, polycystic ovary syndrome, triple negative breast cancer or ovarian cancer. Together, I believe that we will be able to combine our expertise in biology and chemistry to generate quality solutions for hard to tackle or neglected diseases affecting women’s health." stated Pek Lum, Ph.D., CEO of Auransa.

"Quantum Computing technology is coming of age, allowing us to shorten the time to discover new drugs and scale up to multiple targets. We are thrilled to be able to combine our technology with Auransa’s and tackle neglected diseases affecting women. Together, we have unique perspectives on the industry and of unmet needs the pharmaceutical industry can and should tackle, utilizing the best technology available." said Dr. Shahar Keinan, POLARISqb CEO.

On June 4, 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 a poster presentation discussing preliminary data from the Phase 1/2 clinical trial of BDC-1001, Bolt’s lead candidate, was presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held virtually from June 4-8, 2021 (Press release, Bolt Biotherapeutics, JUN 4, 2021, View Source [SID1234618696]). The poster is titled "Preliminary results from a phase 1/2 study of BDC-1001, a novel HER2 targeting TLR7/8 immune-stimulating antibody conjugate (ISAC), in patients (pts) with advanced HER2-expressing solid tumors."

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BDC-1001 is a human epidermal growth factor receptor 2, or HER2, ISAC comprised of a HER2-targeting biosimilar of trastuzumab conjugated to one of Bolt’s proprietary TLR7/8 agonists, for the treatment of patients with HER2-expressing solid tumors, including HER2-low tumors. As of January 29, 2021, Bolt had treated 20 patients and BDC-1001 appeared to be well tolerated with mild to moderate adverse events; no dose-limiting toxicities or drug-related serious adverse events were observed. Clinical activity was seen in the form of stable disease, reductions in tumor volume including a confirmed partial response and increases in pharmacodynamic markers that Bolt believes are consistent with its proposed mechanism of action.

"This poster reinforces the favorable safety and tolerability demonstrated in the first 20 patients treated with BDC-1001 in this first-in-human study in patients with HER2-expressing cancers," said Manish R. Sharma, M.D., of START Midwest, a principal investigator in Bolt’s ongoing BDC-1001 Phase 1/2 trial. "We have seen signs of activity, including a patient with a confirmed partial response and others with stable disease, in a population with diverse tumor types and a median of four prior lines of therapy."

The BDC-1001 Phase 1/2 trial is expected to enroll up to a total of 390 patients and is being conducted in four parts, with dose-escalation dose-expansion parts exploring both monotherapy and combination with a PD-1 checkpoint inhibitor. The monotherapy dose-escalation part of the trial continues to proceed according to plan, and full results are expected to be presented in the second half of 2021. Bolt plans to advance to the monotherapy Phase 2 dose-expansion cohorts and the dose-escalation combining BDC-1001 with an anti-PD-1 antibody later this year.

"I am grateful to everyone on the team for their hard work throughout this trial, especially during the pandemic," said Ecaterina Dumbrava, M.D., of The University of Texas MD Anderson Cancer Center, a principal investigator of the BDC-1001 Phase 1/2 trial. "These initial data provide additional support for the ISAC targeted approach that stimulates both the innate and adaptive immune systems in the treatment of cancer patients."

The abstract and poster from the ASCO (Free ASCO Whitepaper) presentation can be found on the ASCO (Free ASCO Whitepaper) website, as well as on the Bolt website.

About Bolt Biotherapeutics’ Immune-stimulating Antibody Conjugate (ISAC) Platform Technology
The Boltbody ISAC platform technology harnesses the ability of innate immune agonists to convert cold tumors into immunologically hot tumors, thereby illuminating tumors to the immune system and allowing them to be invaded by tumor-killing cells. Boltbody ISACs have demonstrated the ability to eliminate tumors following systemic administration as monotherapy in preclinical models and have also led to the development of immunological memory, which is predicted to translate into more durable clinical responses for patients.

About the Ongoing BDC-1001 Phase 1/2 Study in Patients with HER2-Expressing Solid Tumors
The Phase 1/2, multi-center, open-label study is evaluating the safety, pharmacokinetics, pharmacodynamics and proof of mechanism of BDC-1001 in patients with HER2-expressing solid tumors. The first portion of the study includes a monotherapy dose-escalation phase in which cohorts of patients will receive ascending intravenous doses of BDC-1001 to determine the maximum tolerated dose and/or the recommended dose to advance into expansion cohorts and Phase 2 based on safety and tolerability. The second portion of the study is a dose expansion phase in which patients will receive BDC-1001 monotherapy to further evaluate the safety, tolerability and clinical antitumor activity of the recommended Phase 2 dose. The study also includes similar dose escalation and expansion portions evaluating the combination of BDC-1001 with an anti-PD1 checkpoint inhibitor. Please refer to www.clinicaltrials.gov NCT04278144 for additional clinical trial information.

On June 4, 2021 Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") reported that the Company has entered into an additional collaborative agreement with NextGenNK Competence Center-associated research groups at the Department of Medicine, Huddinge, Karolinska Institutet ("KI") in Stockholm, Sweden, aimed at producing novel cell-based therapeutics using natural killer ("NK") cells derived from induced pluripotent stem cells ("iPSCs") (Press release, Sorrento Therapeutics, JUN 4, 2021, View Source [SID1234583901]). Sorrento and KI are collaborative partners in the Competence Center for the development of next-generation NK cell-based cancer immunotherapies ("NextGenNK") coordinated by KI.

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Under the agreement, Sorrento will provide know-how in the core chimeric antigen receptor ("CAR") and dimeric antigen receptor ("DAR") technologies and support the collaborative effort to develop new CAR-NK and DAR-NK candidates, as well as fund the translational validation of the technologies. Multiple product candidates will be developed and tested in the initial phase of the planned work, with the goal that the candidate products will qualify for further human clinical trials.

The foundational Sorrento research assets critical to this program are novel proprietary CAR and DAR constructs identified through Sorrento’s proprietary G-MAB fully human antibody library and previously validated as determinants of cell-based therapy potency against hematologic and solid tumors.

"It is a privilege to continue and extend our collaborative work with the distinguished KI faculty. We are proud to contribute our technologies to produce new optimized off-the-shelf adoptive NK cell immunotherapies", said Dr. Henry Ji, Chairman and CEO of Sorrento. "Our partnership with KI combines our know-how with the expertise of a world-renowned institution in the field of NK cell therapy. These types of partnerships are essential in advancing medicine and bringing new solutions to cancer patients in need."

KI scientists within NextGenNK will establish iPSC-derived NK-based therapeutic candidates utilizing Sorrento’s constructs and DAR technology. Work within KI has contributed to the development of methodologies that consistently generate robust and potent NK cell lineages following iPSC differentiation. Clinical trials of NK cell-based therapies for treatment of multiple myeloma led by researchers at KI have yielded promising preliminary results with long-lasting remissions. In a very cross-knit collaboration between Sorrento and KI, the team will aim to establish novel allogeneic, off-the-shelf, retargeted NK cell-based therapies.

Utilizing iPSCs enables mass production of off-the-shelf NK cell therapies that leverage Sorrento’s existing manufacturing infrastructure and know-how. Sorrento expects these validated re-engineered NK cell-based therapeutic candidates could potentially become a new generation in off-the-shelf treatments for cancer and infectious diseases. The core research will be performed at Karolinska Institutet with active involvement of the Sorrento R&D team in San Diego.

"The present collaboration brings together key competence from Sorrento and KI in an important area of cancer immunotherapy research. Sorrento’s intellectual contribution to the research at the Competence Center is a critical piece in enabling retargeted off-the-shelf NK cell products", said Evren Alici, Principal Investigator at KI.

"This is an important step in further enabling academic and industrial partnerships in the mission of achieving common goals for advancement of novel cancer immunotherapies," said Hans-Gustaf Ljunggren, Director of the NextGenNK Competence Center.

On June 4, 2021 BerGenBio ASA (OSE:BGBIO), BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical need, reported that end-of-trial data from a Phase I/II study of bemcentinib in combination with erlotinib in patients with advanced non-small cell lung cancer (NSCLC) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, BerGenBio, JUN 4, 2021, View Source [SID1234583870]).

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Study Design

Phase I of the study was a dose escalation arm designed to confirm the safety and tolerability of bemcentinib in NSCLC patients as both monotherapy and in combination with erlotinib in patients whose disease had previously progressed on erlotinib alone.

Phase II assessed patients in two groups; those whose disease had progressed on an approved EGFR inhibitor, and those who were responding/stable on erlotinib as a first line treatment. Both groups were treated with bemcentinib and erlotinib to evaluate the safety and activity of the combination, while assessing reversal or prevention of resistance to EGFR inhibition.

Conclusions

Data from the study found that Bemcentinib in combination with erlotinib was well tolerated over extended periods of time, with the longest ongoing patients having been dosed for over 46 months.

The combination led to disease stabilisation and durable tumour responses in a proportion of patients who had previously progressed on EGFR targeted therapy and who were negative for the T790M resistance mutation. In patients who were responding to first line treatment with erlotinib, either stable disease or partial response, the addition of bemcentinib led to further deepening of responses and prolonged the duration of responses beyond 30 months in 4 out of the 13 patients evaluated.

At the time of data cut-off, 2 patients are still participating in the study beyond 34 months of treatment. Ongoing patients at the time of study closure, who wish to continue receiving study treatment, will be offered the drug via an expanded access program.

Presenting author Lauren Byers, M.D., associate professor of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center, in Houston, said: "We are encouraged by the responses observed both in patients whose disease was progressing on EGFRi alone, as well as patients already in remission with erlotinib. In particular we were pleased to see durable responses exhibited by a number of patients on the study, with two patients continuing to be dosed with bemcentinib beyond 36 months. This is a good indicator that
bemcentinib offers excellent tolerability as well as the potential for anti-tumour activity and we look forward to following their progress as their treatment continues"

Byers reports past advisory board participation for BerGenBio.

Richard Godfrey, CEO of BerGenBio, said: "This end of study data shows the potential of bemcentinib as a combination treatment alongside EGFR inhibitors such as erlotinib and osimertinib, which are established treatments and widely used in indications such as NSCLC in patients with the EGFR driver mutation. We believe that further clinical investigation is needed to fully explore this potential, and look forward to discussing our findings further with our colleagues at ASCO (Free ASCO Whitepaper)."

Details of the presentation, also available on the investor section of BerGenBio’s website, are as follows:

E-poster title: Ph I/II study of oral selective AXL inhibitor bemcentinib (BGB324) in combination with erlotinib in patients with advanced EGFRm NSCLC: end of trial update

Session: Lung Cancer – Non-Small Cell Metastatic

Abstract ID: 9110

Date/Time: Friday, June 4, 2021 at 9:00 AM (EDT)

Authors: Byers et al.

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases.

In COVID-19, AXL has two synergistic mechanisms of action, it acts a co-receptor to ACE2, to which the spike protein of the SARS-CoV-2 virus attaches and enters the host cell, and AXL expression is upregulated that leads to suppression of the Type 1 Interferon immune response by host cells and in their environment.

Research data confirms bemcentinib inhibits SARS-CoV-2 host cell entry and promotes the anti-viral Type I interferon response. Data from a Phase II in human clinical trial has shown that treatment with AXL inhibitor bemcentinib increased the rate ventilator free survival in hospitalised COVID-19 patients.

In cancer, increase in AXL expression has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers. AXL suppresses the body’s immune response to tumours and drives treatment failure across many cancers. High AXL expression defines a very poor prognosis subgroup in most cancers. AXL inhibitors, such as bemcentinib, therefore, have potential high value as monotherapy and as the cornerstone of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases including fibrosis.

About Bemcentinib

Bemcentinib (formerly known as BGB324), is a potential first-in-class, potent and highly selective AXL inhibitor, currently in a broad phase II clinical development programme. It is administered as an oral capsule and taken once per day. Ongoing clinical trials are investigating bemcentinib in COVID-19, and multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent. Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity.