On June 6, 2022 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that results from the Phase II SUMMIT trial, assessing the efficacy of combined neratinib, fulvestrant, and trastuzumab in patients with hormone receptor positive, HER2-negative, HER2-mutant metastatic breast cancer, at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held in person from June 3-7 in Chicago, IL, and online (Press release, Puma Biotechnology, JUN 6, 2022, View Source [SID1234615656]). The poster, entitled "Neratinib + fulvestrant + trastuzumab (N+F+T) for hormone receptor-positive (HR+), HER2-negative, HER2-mutant metastatic breast cancer (MBC): outcomes and biomarker analysis from the SUMMIT trial," was presented at the Breast Cancer — Metastatic Poster Session (poster #1028) by Komal L. Jhaveri, MD, FACP, Medical Oncologist at Memorial Sloan Kettering Cancer Center on June 6 at 9:00 a.m. ET.

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Earlier genomic analyses from a cohort treated with a combination of neratinib and fulvestrant suggest that resistance to neratinib may occur via mutant allele amplification or secondary HER2 mutations. The addition of trastuzumab to the combination of neratinib and fulvestrant in this trial demonstrated positive durable responses in patients with HR-positive, HER2-mutant MBC who had received prior CDK4/6 inhibitors (CDK4/6i).

The Phase II SUMMIT basket trial is an open-label, multicenter, multinational study that included a cohort evaluating the efficacy of the triplet combination of neratinib (N), plus fulvestrant (F), plus trastuzumab (T), in patients with HR-positive, HER2-negative, HER2-mutant metastatic breast cancer, as identified by local genomic sequencing, who had previously received CDK4/6 inhibitors. In order to confirm the contribution of neratinib to the combination, a small, randomized cohort comparing neratinib plus fulvestrant plus trastuzumab versus fulvestrant plus trastuzumab versus fulvestrant was also included. A range of HER2 allelic variants was represented in the cohort. Patients who received the triplet regimen were enrolled in the non-randomized cohort and received 240 mg of neratinib per day intramuscularly, 500 mg intravenous fulvestrant on days 1 and 15 of Cycle 1 and then every 4 weeks, 8mg/kg body weight trastuzumab initially and then 6mg/kg every 3 weeks. Patients in the randomized cohort received either a combination of neratinib, fulvestrant, and trastuzumab, or fulvestrant and trastuzumab, or fulvestrant alone in a 1:1:1 ratio. To counter the side effects of diarrhea, loperamide prophylaxis was mandatory for the first two treatment cycles. Patients who were randomized to the combination of fulvestrant and trastuzumab, or fulvestrant alone, could cross over to receive neratinib, fulvestrant, and trastuzumab at progression. Efficacy was assessed using objective response rate (ORR) and clinical benefit rate (CBR). Tumor tissue was retrospectively assessed by central next-generation sequencing (NGS).

The table below summarizes the efficacy of SUMMIT MBC patients who received neratinib plus fulvestrant plus trastuzumab, those who received fulvestrant plus trastuzumab, and those who received fulvestrant alone; and also those who received fulvestrant plus trastuzumab or fulvestrant and then crossed over to neratinib plus fulvestrant plus trastuzumab upon progression. Patients who received neratinib plus fulvestrant plus trastuzumab (non-randomized + randomized) had a 35.3% investigator-assessed objective response rate, 14.3-month duration of response, 41.7% clinical benefit rate, and 8.2-month median progression-free survival. Neratinib appears to be a critical component of the combination therapy, as demonstrated by lack of response in the small cohort of patients treated with fulvestrant or fulvestrant plus trastuzumab, and by response in a subset of those patients upon crossover to neratinib plus fulvestrant plus trastuzumab.

Table: Efficacy Findings from HR+ Metastatic Breast Cancer Patients

Data cut-off: 15 April 2022. Tumor response based on: investigator tumor assessments (RECIST v1.1)
CR, confirmed response; PR, partial response; CI, confidence interval; DOR, duration of response; NA, not applicable; NE, not estimable; PFS, progression-free survival
a Objective response defined as either a complete or partial response that is confirmed no less than 4-weeks after the criteria for response are initially met;
b Kaplan-Meier analysis. For crossover patients, calculated from time of crossover to N+F+T.
c Clinical benefit is defined as confirmed CR or PR or stable disease (SD) for ≥24 weeks (within +/– 7-day visit window)
These results suggest that the combination of neratinib, fulvestrant, and trastuzumab together is promising for treating HR+ and HER2-mutated MBC with prior exposure to CDK4/6i across a range of HER2 mutations.

Dr. Jhaveri, an investigator of the trial, said, "Patients with hormone receptor-positive, HER2-negative, HER2-mutant metastatic breast cancer who had received prior treatment with CDK4/6 inhibitors demonstrated encouraging clinical activity with durable responses when treated with the triplet combination of neratinib with fulvestrant and trastuzumab. These responses were observed in patients whose tumors harbored a wide spectrum of HER2 mutations, including those with co-occurring HER3 mutations, regardless of ductal or lobular histology, and with a range of HER2 protein expression."

Alan H. Auerbach, Chief Executive Officer, and President of Puma Biotechnology added, "HER2 mutations can be readily and accurately identified and are clinically actionable for targeted therapy in metastatic breast cancers. We are very pleased with the updated activity seen with the combination of neratinib plus trastuzumab plus fulvestrant therapy in this heavily pretreated metastatic breast cancer patient population with HER2-mutated disease."

On June 6, 2022 Onco360, the nation’s leading independent Specialty Pharmacy, reported that it has been selected by Myovant Sciences to be a specialty pharmacy partner for ORGOVYX (relugolix), which is a gonadotropin-releasing hormone (GnRH) antagonist that is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with advanced prostate cancer (Press release, Onco360, JUN 6, 2022, View Source [SID1234615655]).

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"Onco360 is honored to become a specialty pharmacy provider for ORGOVYX patients," said Benito Fernandez, Chief Commercial Officer, Onco360. "We are committed to supporting the highly specialized needs of patients battling advanced prostate cancer across the United States."

According to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program, it is estimated that 268,490 new cases of prostate cancer will be diagnosed in 2022 with a corresponding 34,500 deaths as a result of the malignancy. Prostate cancer is the most commonly diagnosed cancer in male patients. The median age at the time of initial prostate cancer diagnosis is 67 years old with 92.5% of cases occurring in patients who are at least 55 years old. When considering all stages of disease, prostate cancer has a 96.8% five-year overall survival (OS).1

ORGOVYX is commercialized by Myovant Sciences, Inc. and Pfizer, Inc. Please see the full prescribing information for ORGOVYX at Orgovyx Prescribing Information.

On June 6, 2022 Cellworks Group, Inc., a world leader in Personalized Medicine in the key therapeutic areas of Oncology and Immunology, reported results from the myCare-024-04 study, which demonstrate that the Cellworks Singula Therapy Response Index (TRI) was strongly predictive of Overall Survival (OS) and Progression-Free Survival (PFS) for newly diagnosed Glioblastoma Multiforme (GBM) patients (Press release, Cellworks, JUN 6, 2022, View Source [SID1234615654]). In this study, Singula TRI provided patient-specific estimates of OS and PFS for 18 NCCN guideline GBM therapies and provided predictive value beyond physician-prescribed therapy, patient age, patient sex, and MGMT methylation status.

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The results from the myCare-024-04 clinical study were featured in a poster presentation with comments from Dr. Manmeet Ahluwalia, M.D., M.B.A., Chief of Medical Oncology, Chief Scientific Officer and Deputy Director at Miami Cancer Institute, part of Baptist Health South Florida, at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting June 3-7th during the Central Nervous Systems Tumors Session and available online as Abstract 2053.

"The molecular heterogeneity of GBM is a key driver for the inconsistent therapy response rates that we see in brain cancer patients and makes the disease difficult to treat," said Patrick Wen, MD, Director, Center for Neuro-oncology, Dana-Farber Cancer Institute; Professor, Neurology, Harvard Medical School; and Co-Principal Investigator for the myCare-024-04 clinical study. "But by using a patient’s NGS data and Cellworks Singula to biosimulate their individual therapy responses, we can potentially improve the ability to select the most effective therapy for each GBM patient and positively effect clinical outcomes for brain cancer patients."

"The significant differences in treatment response among GBM patients necessitates moving beyond population-based treatments to personalized multi-gene therapy predictions," said Dr. Manmeet Ahluwalia, M.D., M.B.A., Chief of Medical Oncology, Chief Scientific Officer and Deputy Director at Miami Cancer Institute, part of Baptist Health South Florida; and Co-Principal Investigator for the myCare-024-04 clinical study. "Using Cellworks Singula TRI, we can simulate the molecular effects of cell signaling, drugs and radiation on patient-specific in silico diseased cells prior to treatment and then identify the magnitude of disease control and survival for specific anti-tumor strategies. The findings from using this approach in the myCare-024-04 study suggest that biosimulating guideline GBM therapies for newly diagnosed GBM patients can positively effect clinical outcomes."

The Cellworks Biosimulation Platform simulates how a patient’s personalized genomic disease model will respond to therapies prior to treatment and identifies novel drug combinations for treatment-refractory patients. The platform is powered by the groundbreaking Cellworks Computational Omics Biology Model (CBM), a network of 7,000+ human genes, 30,000+ molecular species and 100+ signaling pathways. As part of the biosimulation process, personalized disease models are created for each patient using their cytogenetic and molecular data as input to the Cellworks CBM. The Cellworks platform analyzes the impact of specific therapies on the patient’s personalized disease model and generates a Singula biosimulation report with Therapy Response Index (TRI) scores from 0 to 100 that predict the efficacy of specific chemotherapies.

myCare-024-04 Clinical Study

Background

In this study, the Cellworks Singula Therapy Response Index (TRI) was used to prospectively predict the Overall Survival (OS) and Progression-Free Survival (PFS) in a retrospective cohort of 270 IDH wildtype GBM patients from the Cancer Genome Atlas (TCGA) with known clinical outcomes treated with physician prescribed therapies. The cohort included 162 males and 108 females with a median age of 57.5 years.

Methods

A mechanistic mulit-omcis biology model created for each patient using comprehensive genomic inputs allows biosimulation of downstream molecular effects of cell signaling, drugs and radiation on a patient’s personalized in silico disease model. Stratified random sampling was used to split the data into independent training (N=153) and validation (N=117) subjects. Multivariate Cox Proportional Hazard and Proportional Odds models were used to model OS and PFS as a function of the pre-defined Singula TRI and clinical thresholds. Cox Proportional Hazards (PH) regression and likelihood ratio (LR) tests were used on the independent validation subjects to assess the hypothesis that Singula is predictive of OS and PFS above and beyond standard clinical factors.

Results

Using Cellworks Personalized Therapy Biosimulation, Singula TRI was significantly predictive of OS and PFS in univariate analyses and remained significantly predictive in multivariate analyses, which included patient age, patient sex, MGMT methylation status and drug class.

Conclusions

Cellworks Singula TRI facilitates selection of optimal personalized therapies by providing patient-specific estimates of OS and PFS for 18 NCCN guideline GBM therapies. This information may be used to estimate increases in OS and PFS when comparing Singula TRI recommended therapies verses standard care. These positive results suggest the utility of biosimulation-informed therapy selection to improve survival of GEA patients.

On June 6, 2022 National Resilience, Inc. (Resilience), a technology-focused biomanufacturing company dedicated to broadening access to complex medicines, reported it has raised $625 million in a Series D financing, in addition to a previously unannounced $600 million Series C financing completed in August 2021 (Press release, National Resilience, JUN 6, 2022, View Source [SID1234615653]).

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The company will use the funding to continue to invest in building its infrastructure network through strategic collaborations, acquisitions, organic growth and international expansion, and by developing innovative biomanufacturing technologies to ensure the medicines of today and tomorrow can be made quickly, safely and at scale. Resilience is also investing in advanced R&D, including stable cell lines for viral vector production, distributed manufacturing for autologous cell therapy and cell-free and continuous manufacturing for biologics.

"We have an ambitious goal to reinvent biomanufacturing by bringing new processes and technologies to an industry that hasn’t kept pace with the explosive innovation in drug discovery," said Rahul Singhvi, Sc.D., Chief Executive Officer of Resilience. "While we recognize that our goal is neither quick nor easy, we are driven by our mission to democratize access to medicines. These new funds will help support our next phase of growth, as we continue to innovate biomanufacturing across all our modalities, expand our footprint to serve customers, sign strategic collaborations and support the developers of a new generation of complex medicines."

Resilience, which focuses on five therapeutic modalities – biologics, vaccines, nucleic acids and cell and gene therapies – currently has 10 facilities across North America, with more than 1 million square feet of manufacturing space and more than 1,600 employees. The company’s network, which is expected to add capacity and capabilities this year with projects underway at several existing sites, is agile enough to scale customer projects from process and analytical development through preclinical to large scale commercial drug substance and drug product manufacturing.

Resilience‘s flexible business model enables it to partner with customers of any size and across therapeutic modalities, through fee-for-service arrangements, value-share agreements and new company creation/incubation projects. The company also provides opportunities for early access and out licensing of next-generation technologies. Beyond industry customers and partners, Resilience works with government agencies, academic institutions and non-profit organizations.

The latest up-round financing was led by new and existing investors, including venture capital funds, public mutual funds, pension funds, biopharma companies, sovereign wealth funds and private family offices, among others. In total, Resilience has secured more than $2 billion in equity financing since its founding in 2020.

Recent Notable Milestones and Developments

Technology:

Acquired SwiftScale Biologics, a company developing cell-free protein synthesis, a technology that aims to eliminate the constraints of using living cells in the drug manufacturing process, resulting in faster production times, less variability across batches and greater scalability with hard-to-produce proteins.
Customers:

Established a multi-product development and manufacturing collaboration with Takeda’s Plasma-Derived Therapies Business Unit.
Secured a contract with the U.S. Department of Defense for manufacturing a monoclonal antibody as a medical countermeasure to botulinum neurotoxins.
Signed a strategic manufacturing services agreement with Opus Genetics, a gene therapy company developing treatments for inherited retinal diseases.
Manufacturing Infrastructure:

Acquired bluebird bio’s Research Triangle manufacturing facility in North Carolina.
Added capacity and capabilities including drug substance and drug product manufacturing expansions coming online in 2022 across sites in Alachua, FL, Boston and Toronto, to support biologics and vaccines.
Constructing a new, state-of-the-art facility in Marlborough, MA to support vaccines and gene therapy, coming online in 2023.
Adding a new cell and gene therapy process and analytical development as well as drug substance manufacturing site in the Philadelphia region.
Academic Collaborations & Incubations:

Launched a joint venture with The University of Texas MD Anderson Cancer Center to accelerate the development and manufacturing of innovative cell therapies for patients with cancer.
Entered into a five-year R&D alliance with Harvard University to incubate new technologies and launch companies to advance the manufacture of complex medicines.
Formed a strategic collaboration with Children’s Hospital of Philadelphia (CHOP) to implement next-generation biomanufacturing technologies and capabilities aimed at accelerating the creation of impactful therapies and technologies for the benefit of patients.
Value-Share Agreements:

Formed a strategic collaboration with Be Biopharma to manufacture engineered B Cells to create a new class of autologous and allogeneic cellular medicines.

On June 6, 2022 Cellworks Group, Inc., a world leader in Personalized Medicine in the key therapeutic areas of Oncology and Immunology, reported results from the myCare-004 study, which demonstrate that the Cellworks Singula Therapy Response Index (TRI) is highly predictive of Overall Survival (OS), Disease-Free Survival (DFS) and Mandard-tumor regression grade (TRG) for gastroesophageal adenocarcinoma (GEA) patients (Press release, Cellworks, JUN 6, 2022, View Source [SID1234615652]). In this retrospective study, Singula TRI provided additional predictive information for OS and DFS beyond patient age, patient gender and physician-prescribed treatment.

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The results from the myCare-004 clinical study were featured in a poster session as part of the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting during the Gastrointestinal Cancer – Gastroesophageal Pancreatic and Hepatobiliary Track and available online as Abstract 4064.

"This study confirmed that there are many dysregulated signaling pathways responsible for hallmark behaviors of cancer and variable drug response in gastroesophageal adenocarcinoma patients," said Dr. Elizabeth Smyth, Cambridge University Hospitals NHS Foundation Trust and Co-Principal Investigator of the myCare-004 clinical study. "Cellworks personalized therapy biosimulation enables us to utilize a patient’s comprehensive next generation sequencing (NGS) results and understand the downstream molecular effects of specific drugs on cell signaling to predict how each patient will respond to therapies prior to treatment. The next step is to evaluate whether biosimulation-informed therapy selection can be used prospectively to improve the survival of GEA patients."

"Gaining a better understanding of the molecular determinants of gastroesophageal adenocarcinoma is key to improving therapy response rates for GEA patients," said Dr. Rebecca Fitzgerald, MD, Professor of Cancer Prevention at the University of Cambridge; Director of the CRUK Cambridge Centre Early Detection Institute; and Co-Principal Investigator of the myCare-004 clinical study. "There are limited treatment options for this cancer type and we look forward to testing the Cellworks personalized therapy predictions in a prospective trial."

The Cellworks Biosimulation Platform simulates how a patient’s personalized genomic disease model will respond to therapies prior to treatment and identifies novel drug combinations for treatment-refractory patients. The platform is powered by the groundbreaking Cellworks Computational Omics Biology Model (CBM), a network of 7,000+ human genes, 30,000+ molecular species and 100+ signaling pathways. As part of the biosimulation process, personalized disease models are created for each patient using their cytogenetic and molecular data as input to the Cellworks CBM. The Cellworks platform analyzes the impact of specific therapies on the patient’s personalized disease model and generates a Singula biosimulation report with Therapy Response Index (TRI) scores from 0 to 100 that predict the efficacy of specific chemotherapies.

myCare-004 Clinical Study

Background

In this study, the Cellworks Singula Therapy Response Index (TRI) was used to prospectively predict the Overall Survival (OS), Disease Free Survival (DFS) and Mandard-tumor regression grade (TRG) in a retrospective cohort of gastroesophageal adenocarcinoma patients from the UK OCCAMS consortium. 271 GEA patients were selected who had pre-chemo treated biopsies with 50x whole genome sequencing. 234 patients were male and 30 female with a median age of 65.6 years. Within the study population, there were 35 T2, 215 T3, 70 N0, 126 N1, 62 N2 and 266 M0. Patients were prescribed chemotherapy treatments according to UK clinical guidelines.

Methods

A mechanistic model created for each patient using comprehensive genomic inputs biosimulated downstream molecular effects of cell signaling and drugs for a patient’s personalized in silico disease model. Random sampling stratified by clinical factors was used to split the data into independent training (N=140) and validation (N=131) subsets. Multivariant Cox Proportional Hazard (PH) and Proportional Odds models were used to predict survival and pathological response as a function of the pre-defined Therapy Response Index (TRI) and clinical thresholds compared with standard clinical factors.

Results

Cellworks Personalized Therapy Biosimulation found that 99% of the patients’ tumors had deficiency in DNA repair genes. Other pathways included amplification of multi-drug resistance pumps, TP53 mutations and aberrations of the PI3K/AKT pathway genes. Cellworks Singula Therapy Response Index (TRI) provided additional predictive information for OS and DFS beyond physician prescribed treatment and standard clinical factors. TRI was also predictive of TRG in univariate analysis. TRI scores were generated for 82 alternate therapies for each patient, enabling selection of optimal therapies with estimates of improvements in median OS and DFS compared to standard care (SC).

Conclusions

The study found that Cellworks Singula TRI was predictive of Overall Survival (OS), Disease-Free Survival (DFS) and Mandard-tumor regression grade (TRG) beyond clinical factors in this cohort of gastroesophageal adenocarcinoma (GEA) patients. These positive results suggest the utility of biosimulation-informed therapy selection to improve survival of GEA patients.