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.

On June 6, 2022 SOPHiA GENETICS (Nasdaq: SOPH), the creator of a global data pooling and knowledge sharing platform that advances data-driven medicine, reported an update on its multimodal DEEP-Lung-IV clinical study (NCT04994795) at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Sophia Genetics, JUN 6, 2022, View Source [SID1234615668]). This will be discussed during the company’s joint Innovation Symposium with GE Healthcare Monday, June 6th from 6:30 – 8:00 pm CDT.

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Immunotherapy has revolutionized the management of metastatic non-small cell lung cancer. Despite its promise, the majority of patients fail to respond to the therapy while being exposed to potentially severe side effects. Existing biomarkers are suboptimal as they do not allow to predict which patients will benefit from the therapy. There is an urgent need to identify biomarkers that are predictive of response to immunotherapy at the individual patient level.

New agreement signed with GE Healthcare to utilize Imaging Fabric to further accelerate radiomics analysis workflows

SOPHiA GENETICS launched the DEEP-Lung-IV clinical study to leverage its multimodal machine learning-powered analytics capabilities to identify multimodal predictive signatures of response to immunotherapy for patients with advanced lung cancer. Through its global footprint, the study is intended to maximize exposure of the machine learning algorithms to a wide range of diverse, real-world data. Insights from the DEEP-Lung-IV study will power one of the applications of the CarePath module of the SOPHiA DDMTM platform, offering advanced data visualization, cohorting, and predictive capabilities in a single solution.

To date, 19 sites across seven countries have signed up for participation in the study, including Roswell Park Comprehensive Cancer Center in New York. "I am personally very excited to join the DEEP-Lung-IV study. I see tremendous value in the multimodal machine learning-powered approach to real-world data analytics and look forward to potentially applying it to other clinical questions of high relevance in lung cancer", said Dr. Prantesh Jain, Assistant Professor of Oncology at Roswell Park Comprehensive Cancer Center. Together, these sites have already recruited over 500 patients.

Early findings are promising and conceptually validate the potential for multimodal signatures to predict response to immuno-chemotherapy at the individual patient level. First results will be discussed during SOPHiA GENETICS’ joint Innovation Symposium with GE Healthcare on Monday, June 6, at 6:30 pm CDT.

"We are very excited by the strong operational traction in recruiting patients to the study, as well as the promising early findings. With its unique machine learning-powered multimodal study design and its focus on collecting very diverse real-world data from lung cancer patients around the world, we feel that the DEEP-Lung-IV study has the potential to usher a new era of precision medicine that would enable predictions at the individual patient level. We look forward to further validating our vision of building a multimodal decentralized collective intelligence, leveraging on real-world data to generate novel insights at the individual patient level," said Dr. Philippe Menu, SVP & Chief Medical Officer, SOPHiA GENETICS.

SOPHiA GENETICS has also entered into an agreement with GE Healthcare to utilize their Imaging Fabric Core and Imaging Fabric Annotation Template, as part of the Edison Digital Health Platform. In the context of the DEEP-Lung-IV clinical study, Imaging Fabric services will be used to visualize, segment, and annotate lung lesions for medical imaging visualization and annotation purposes. This allows SOPHiA GENETICS to further accelerate proprietary radiomics analytics workflows in the context of the study, in particular to move towards automatic whole-body tumor identification, segmentation, and quantification.

"We’re eager to further strengthen our collaboration with SOPHiA GENETICS. The use of Imaging Fabric and the SOPHiA DDMTM Platform are key to create the world of tomorrow, in which we aim to jointly break data silos across data modalities to deliver insights to physicians to help them optimize patient treatment workflows. We look forward to seeing how the DEEP-Lung-IV study results can help improve outcomes for those diagnosed with lung cancer," said Ben Newton, MD, General Manager, GE Healthcare Oncology Solutions.

SOPHiA GENETICS’ DEEP-Lung-IV clinical study aims to predict immunotherapy treatment response upon first evaluation at the individual patient level using data across multiple modalities including genomics, radiomics, clinical, and biological data. The study also aims to validate an algorithm that will allow the prediction of outcomes of the individual patient such as progression-free survival (PFS) and overall survival (OS). This predictive model will help identify patients that are likely to benefit from immunotherapy versus those that are not. It will stratify patients according to risk, helping clinicians make more informed therapeutic decisions for their patients, supporting biopharma to ensure the right patients are selected for clinical trials.

On June 6, 2022 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported an update to its strategic priorities and the streamlining and realignment of resources to support its key value-generating indications and programs and extend its estimated cash runway into late 2024 (Press release, Vincerx Pharma, JUN 6, 2022, View Source [SID1234615685]).

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Strategic Update Summary:

Prioritizing VIP152 clinical studies to focus on:
Monotherapy in patients with high grade B-cell lymphoma characterized by translocations of MYC and BCL-2 or BCL-6 (aka double-hit diffuse large B-cell lymphoma [DLBCL])
Monotherapy in patients with high-risk chronic lymphocytic leukemia (CLL)
Combination with Bruton tyrosine kinase (BTK) inhibitor in patients with high-risk CLL
Continuing to prioritize advancement of first-in-class and potentially best-in-class bioconjugation assets
Streamlining and realigning resources to support prioritized VIP152 indications and advancement of the bioconjugation programs
Reducing full-time employees by 33%
Implementing additional cost reduction measures
Extending estimated cash runway into late 2024
Positioning company to continue executing on important clinical and preclinical milestones
"Given the unprecedented market conditions, we are making a strategic decision to focus our resources on our ongoing double-hit DLBCL and CLL clinical trials and our next-generation bioconjugation platform to deliver the greatest benefit in these patients as well as maximize value for our shareholders," said Ahmed Hamdy, M.D., Chief Executive Officer of Vincerx.

"The VIP152 program was designed as a signal-seeking program," added Dr. Hamdy. "Nineteen (19) patients with various MYC+ cancers have been treated. We saw stable disease in 3 patients with ovarian cancer (with one of the three patients completing cycle 6). Despite this preliminary signal in ovarian cancer, the combination of challenging market conditions and the promising VIP152 preclinical and clinical data we have seen in double-hit DLBCL and CLL patients create a compelling rationale for us to focus our efforts on these two indications."

"We continue to be excited about our preclinical bioconjugation platform—a diverse, modular platform of linkers and payloads that can be conjugated with antibodies and small molecules to create novel targeted therapeutics for a broad range of solid tumors and hematologic malignancies and remain on track to file an IND in the second half of this year for VIP236. We also remain on track to file an IND in the second half of 2023 for our initial antibody drug conjugate (ADC), VIP943. We believe our ADCs represent a paradigm-shifting technology with a proprietary and highly differentiated linker and warhead. These innovations are expected to improve efficacy and safety versus current ADCs," continued Dr. Hamdy.

To support this strategy, Vincerx also announced the streamlining and realignment of resources and the implementation of certain cost reduction measures, including a 33% reduction of full-time employees. "Reducing our staff was not an easy decision. It was the tremendous effort of our Vincerx colleagues that allowed us to execute efficiently, despite the extreme pressures of the pandemic. I want to sincerely thank every Vincerx colleague who has been impacted by this realignment. Their contributions have, without a doubt, brought us closer to achieving our goals. The realignment announced today will allow us to focus on and invest in the indications and programs we believe will generate the greatest value while reducing our operating expenses—all with the goal of achieving our anticipated key milestones for VIP152 and our bioconjugation platform," concluded Dr. Hamdy.

CLINICAL UPDATES

VIP152 (as of April 19, 2022):

VNC-152-101 study enrollment (Patients with MYC+ cancer, which included overexpression, translocation, deletion, or amplification):
High-grade lymphoma arm (n=4)
Histologies: triple-hit, double-hit, double expressor and primary mediastinal (n=1 each)
Gynecologic malignancies (n=5)
Includes 1 patient with endometrial cancer who received combination therapy of VIP152 + pembrolizumab
Triple negative breast cancer (n=2)
Tumor agnostic group (n=7)
Consists of various types of gastrointestinal cancer (n=6) and melanoma (n=1)
VNC-152-102 study enrollment:
CLL that has failed BTK inhibitor therapy, as well as venetoclax therapy (n=1)
Clinical outcomes from VNC-152-101 and VNC-152-102:
No new safety signals were identified; manageable treatment-related adverse events included neutropenia and gastrointestinal toxicity (i.e., nausea, vomiting and diarrhea); only 1 patient discontinued due to an adverse event (i.e., Grade 1 nausea)
Progressive disease was observed in 16 patients, despite evidence of tumor shrinkage in some patients including the patient with CLL who had failed BTK inhibitor and venetoclax therapy. Best response in all 19 patients has been stable disease in 3 patients with ovarian cancer as reported at the AACR (Free AACR Whitepaper) Annual Meeting in 2022.
Abstract accepted for poster presentation at the upcoming European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting, titled "VIP152 is a novel CDK9 inhibitor with improved selectivity, target modulation, and cardiac safety in patients with lymphoma."
Presenting author: Melanie Frigault, PhD
Abstract number: P1269
Session date and time: Friday, June 10, 2022; 16:30-17:45 CEST

Bioconjugation Platform:

Continue to advance next-generation modular bioconjugation platform, comprised of a first-in-class SMDC for solid tumors (VIP236) and two potentially best-in-class assets for hematologic malignancies (VIP943 and VIP924)
VIP236: IND filing in solid tumors expected in 2H 2022
VIP943 (anti-CD123) and VIP924 (anti-CXCR5): Manufacturing is underway and IND filing for VIP943 expected in 2H 2023 and VIP924 in 2024

On June 6, 2022 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing first-in-class allogeneic gamma delta chimeric antigen receptor (CAR) T cell therapies for cancer, reported emerging positive safety and efficacy data from the Company’s Phase 1 study of ADI-001 for the potential treatment of relapsed or refractory B-cell Non-Hodgkin’s Lymphoma (NHL) in an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 6, 2022 (Press release, Adicet Bio, JUN 6, 2022, View Source [SID1234615620]). The presentation outlines a summary of clinical data as of a May 31, 2022, data-cut date.

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"Adicet is a pioneer in the field of gamma delta CAR T cell therapies and it is gratifying to see the highly encouraging clinical data for ADI-001 unfold as a potential best-in-class therapy for NHL," said Chen Schor, President and Chief Executive Officer of Adicet Bio. "Notably, with a favorable safety and tolerability profile, treatment to date with ADI-001 demonstrated an impressive CR rate, including 100% in CAR-T relapsed patients, and very encouraging durability of response. We look forward to discussing the data in more detail and outlining next steps in our webcast this afternoon."

"It is impressive to see 50 percent of six-month evaluable patients cancer free beyond seven months. One of these patients had previously relapsed after two treatments with autologous anti-CD19 CAR T and now remains cancer free seven and a half months following administration of ADI-001, suggesting the patient has had major clinical benefit from ADI-001. This is particularly notable because patients who relapse after autologous anti-CD19 CAR T have dismal outcomes with a median survival of approximately six months," said Sattva Neelapu, M.D., Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. "When we look at the totality of these early data, we have an indicator that allogeneic gamma-delta CAR T cell therapy like ADI-001 could be a significant advance."

"NHL remains a disease that is very difficult to treat, especially in high-risk patients with aggressive disease. Our study is enrolling patients with aggressive B-cell lymphoma, including patients with double-hit and triple-hit high-grade B cell lymphoma and patients who had a prior relapse to autologous anti-CD19 CAR T therapy," said Francesco Galimi, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Adicet Bio. "We are encouraged by the CRs observed to date in the Phase 1 study and are committed to rapidly advancing ADI-001 into a potential pivotal program."

Data highlights as of the May 31, 2022 data-cut date included in the ASCO (Free ASCO Whitepaper) presentation are as follows:

Of the eight evaluable patients, three received ADI-001 at dose level 1 (30 million CAR+ cells), three received ADI-001 at dose level 2 (100 million CAR+ cells) and two received ADI-001 at dose level 3 (300 million CAR+ cells). There are currently no patients with indolent lymphoma, such as follicular lymphoma, enrolled in the study.
Patients were heavily pretreated with a median number of prior therapies of 4 (range 2-5) and had a poor prognostic outlook as indicated by the median International Prognostic Index (IPI) score of 4 (range 2-5).
ADI-001 treatment demonstrated a 75% overall response rate (ORR) and complete response (CR) in the study across all dose levels. In dose levels 2 and 3 combined, ADI-001 demonstrated an 80% ORR and CR rate.
In three patients that previously relapsed after prior autologous anti-CD19 CAR T therapy, treatment with ADI-001 demonstrated 100% ORR and CR rate. These patients included a triple-hit high grade B-cell lymphoma patient with prior exposure to Liso-cel, as well as a DLBCL patient and a double-hit high grade B-cell lymphoma patient who had previously achieved a PR to Axi-cel.
Early data indicate encouraging durable anti-tumor responses with potential for dose related increase in durability. 50% (2 of 4) of evaluable patients with at least six months follow up remain cancer free.
Detection of circulating ADI-001 in the blood by flow cytometry indicated in vivo expansion and dose-related increase of ADI-001 exposure in patients.
ADI-001 was well tolerated in the study to date. There were no occurrences of dose-limiting toxicities, graft vs host disease (GvHD), or Grade 3 or higher Cytokine Release Syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) reported. There were no infections associated with enhanced lymphodepletion (eLD).
Table 1: Summary of ADI-001 interim data from three dosing cohorts: *

*Efficacy-evaluable patients as of the May 31, 2022 data-cut date. Data are subject to further review and verification. BOR= best overall response. PD=progressive disease.

Table 2: ADI-001 Preliminary Efficacy Data:
(Per protocol analysis, independent radiographic assessment using Lugano 2014)

*Efficacy-evaluable patients as of the May 31, 2022, data-cut date. Data are subject to further review and verification.

As of the May 31, 2022, data-cut date, of the six patients who achieved CR:

Dose level 1:

As previously disclosed, one patient administered ADI-001 in dose level 1, a 66-year-old female who had achieved a CR, developed COVID-19 related pneumonia approximately two and a half months after ADI-001 administration and later died of complications from it, unrelated to ADI-001. This patient was previously reported as a partial response (PR) by local radiological assessment and has been assessed as a CR by independent central reading.

One patient with triple-hit high grade B-cell lymphoma in dose level 1 who had relapsed following two prior treatments with autologous anti-CD19 CAR T therapy, had a CR after treatment with ADI-001. The patient developed a local skin relapse at four months, and was administered local radiotherapy. The skin lesion resolved with no systemic therapy provided to the patient. The patient continues to be cancer free seven and a half months following administration of ADI-001, as measured by a negative PET/CT scan.

Dose level 2:

Both patients administered ADI-001 in dose level 2 have ongoing CR. One patient has a CR beyond seven months and one patient has a CR beyond four and a half months.

Dose level 3:

Both patients administered ADI-001 in dose level 3 have ongoing CR with follow-up beyond three and one month, respectively.

In summary, 50% of evaluable patients with at least six months follow up (2 of 4) remain cancer free.

Table 3: ADI-001 Preliminary Safety Data in Efficacy-Evaluable Patients+

+Safety assessment was performed using the Common Terminology Criteria for Adverse Events (v5) and the American Society for Transplantation and Cellular Therapy criteria. The two ADI-001-related adverse events of special interest (AESI) were a Grade 1 CRS at DL1 and a Grade 1 ICANS at DL2, which resolved within 24 hours without medical intervention​; No DLTs or GvHD; No treatment discontinuations due to AEs​; two patients administered standard lymphodepletion (sLD) and six patients eLD​; There were no eLD-associated clinical infection.

*One patient in DL 1 who received sLD developed COVID-19 pneumonia later died of complications of it, unrelated to ADI-001.

Given the safety profile to date, the protocol was amended to include a new DL 4 (1E9 CAR+ cells) and a potential ADI-001 consolidation dosing at DL3 to finalize the recommended Phase 2 dose in the second half of 2022. The Company expects to provide at least one additional clinical update for the ADI-001 Phase 1 study in the second half of 2022. The Company will discuss with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) the design of two pivotal intent studies and a potential path to support a Biologics License Application (BLA) and Marketing Authorization Application (MAA) for ADI-001 and initiate at least one potentially pivotal study in the first half of 2023.

Details of the ASCO (Free ASCO Whitepaper) Oral Presentation:

Abstract Number: 7509
Abstract Title: A Phase 1 Study of ADI-001: Anti-CD20 CAR-engineered Allogeneic Gamma Delta (γδ) T cells in Adults with B-cell Malignancies
Presenting Author: Sattva Neelapu, M.D., The University of Texas MD Anderson Cancer Center
Session Type/Title: Clinical Science Symposium/ Beating Bad Blood: The Power of Immunotherapy in Hematologic Malignancies
Date: Monday, June 6, 2022
Time: 8:00 AM-9:30 AM CDT

Webcast/ Conference Call information

The Company will host a conference call and webcast today, June 6, 2022, at 4:30pm ET to discuss the results. The live webcast of the presentation can be accessed under "Presentations & Events" in the investors section of the Company’s website at www.adicetbio.com or by dialing (877) 800-3802 (domestic) or +1 (615) 622-8057 (international) and referencing the conference ID 5466375. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

About ADI-001

ADI-001 is an investigational allogeneic gamma delta CAR T cell therapy being developed as a potential treatment for relapsed or refractory B-cell NHL. ADI-001 targets malignant B-cells via an anti-CD20 CAR and via the gamma delta innate and T cell endogenous cytotoxicity receptors. Gamma delta T cells engineered with an anti-CD20 CAR have demonstrated potent anti-tumor activity in preclinical models, leading to long-term control of tumor growth. In April 2022, ADI-001 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the potential treatment of relapsed or refractory B-cell NHL.

About the GLEAN Study

This Phase 1 study is an open-label, multi-center study of ADI-001 enrolling adults diagnosed with B-cell malignancies who have either relapsed, or are refractory to at least two prior regimens. The primary objectives of the study are to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ADI-001, and to determine optimal dosing as a monotherapy. The study is expected to enroll approximately 75 patients. For more information about the clinical study design, please visit www.clinicaltrials.gov (NCT04735471).

On June 6, 2022 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported results of a prospective analysis from the Phase 1b cohort of the KRYSTAL-1 study evaluating intracranial (IC) responses of adagrasib in patients with KRASG12C-mutated non-small cell lung cancer (NSCLC) with active and untreated central nervous system (CNS) metastases (Press release, Mirati, JUN 6, 2022, View Source [SID1234615636]). This is the first clinical data demonstrating CNS-specific activity of a KRASG12C inhibitor in patients with NSCLC with active and untreated CNS metastases. Findings show that approximately one third of the patients had an IC response in patients with CNS metastases, consistent with what was observed systemically in this cohort.

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The data will be presented today as a late-breaking oral presentation in the session titled, "Clinical Science Symposium/Including the Excluded: Advancing Care for All Patients With Lung Cancer" at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from 5:30 to 5:42 PM ET/4:30 to 4:42 PM CT (Abstract #LBA9009).

"We are proud to share the first clinical data demonstrating CNS-specific activity of a KRASG12C inhibitor in patients with NSCLC," said Charles Baum, M.D., Ph.D., president, founder and head of research and development, Mirati Therapeutics, Inc. "Central nervous system metastases disproportionately affect patients with NSCLC and should be carefully considered as part of the treatment approach. Adagrasib showed CNS penetration and intracranial responses in patients with active and untreated CNS metastases, demonstrating potential as a treatment option for this underserved patient population."

Results of Prospective Analysis

With a median follow up of 6.6 months (data cutoff date December 2021), 25 patients with active, untreated CNS metastases were enrolled in the study and treated with adagrasib 600 mg BID.

Of the radiographically evaluable patients (n=19), results showed an IC objective response rate of 32% (6/19) by modified response assessment in neuro-oncology-brain metastases (modified RANO-BM) by blinded independent central review.

In this analysis, three patients achieved a complete response and three patients achieved a partial response. The IC disease control rate was 84% (16/19, including 10 patients with stable disease). The median IC duration of response was not reached (95% confidence interval: 4.1 – not evaluable). Concordance of disease control between systemic and IC responses was 88% (14/16). For all patients enrolled, median overall survival was not reached.

Cerebrospinal fluid (CSF) samples were obtained from two patients for whom regression of CNS metastases was observed; adagrasib CSF/free plasma concentration ratios (Kp,uu: 0.47) were consistent with other agents with known CNS penetration and activity.

The safety profile of adagrasib in this study was consistent with the overall population with no new safety signals observed. Grade 1 and 2 treatment related adverse events (TRAEs) occurred in 60% of patients. Grade 3 TRAEs occurred in 36% of patients, and there were no Grade 4/5 TRAEs.
"Central nervous system metastases occur in 27% to 42% of patients with KRASG12C-mutated NSCLC at diagnosis. These patients have a median overall survival of approximately five months, posing a serious clinical challenge," said Joshua K. Sabari, M.D., assistant professor of medicine, medical oncology at Perlmutter Cancer Center, NYU Langone Health. "With a median follow up of 6.6 months, these early and positive data show adagrasib demonstrated a meaningful overall intracranial response rate with early indications for overall survival. Adagrasib warrants further investigation on its potential to improve clinical outcomes for NSCLC patients harboring a KRASG12C-mutation who have active and untreated CNS metastases, including opportunities through Mirati’s Expanded Access Program."

Mirati also presented results from the registration-enabling Phase 2 cohort of the KRYSTAL-1 study evaluating adagrasib in patients with pre-treated NSCLC harboring a KRASG12C mutation during the Lung Cancer–Non-Small Cell Metastatic session at ASCO (Free ASCO Whitepaper) on June 3, 2022.

Virtual Investor Event

Mirati Therapeutics will host an Investor Event on Monday, June 6, 2022, at 8:00 PM ET/ 7:00 PM CT.

Company executives will provide an overview of the adagrasib clinical data presented at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting and the Company’s broader lung cancer strategy, including in earlier lines of therapy.

Investors and the general public are invited to register and listen to a live webcast of the event through the "Investors and Media" section on Mirati.com. A replay of the event will be available shortly after the conclusion of the event.

Central Nervous System (CNS) Metastases in KRAS-Mutated Lung Cancer

The brain, along with the bone, adrenals, and liver are common sites of extra-thoracic metastases in NSCLC.[1]−3 CNS metastases occur in 27−42% of patients with KRASG12C-mutated NSCLC at diagnosis.1,4−6 Additionally, patients with CNS metastases and KRAS-mutated NSCLC may have poor outcomes, with median overall survival ranging of approximately five months. 7-9

About Adagrasib (MRTX849)

Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24–48 hours. Adagrasib is being evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including NSCLC, colorectal cancer and pancreatic cancer. For more information visit Mirati.com/science.

Mirati has an Expanded Access Program (EAP) for investigational adagrasib for the treatment of eligible patients with KRASG12C-mutated cancers, regardless of tumor type, including patients with treated or untreated CNS metastases, in the U.S. Learn more about the EAP at Mirati.com/expanded-access-policy.