On November 6, 2023 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported financial results and operational updates for the quarter ended September 30, 2023 (Press release, ORIC Pharmaceuticals, NOV 6, 2023, View Source [SID1234637042]).

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"We continued making strong progress across our pipeline in the third quarter of 2023 with steady enrollment across our three clinical trials and the first presentation of clinical data for ORIC-114," said Jacob M. Chacko, MD, chief executive officer. "Initial data for ORIC-114 demonstrated clinical activity across multiple dose levels, including the first reported CNS complete response by an EGFR exon 20 inhibitor in a patient with untreated brain metastases, and a favorable safety profile. We are eager to continue advancing ORIC-114, and we also look forward to presenting initial clinical data for ORIC-533 in multiple myeloma and for ORIC-944 in prostate cancer over the coming quarters."

Third Quarter 2023 and Other Recent Highlights:

ORIC-114: a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor

Presented initial data from the ongoing Phase 1b dose escalation trial for patients with EGFR or HER2 exon 20 mutated non-small cell lung cancer (NSCLC) at the ESMO (Free ESMO Whitepaper) Congress 2023.
CNS activity was observed at multiple dose levels, including the first reported CNS complete response by an EGFR exon 20 inhibitor in a patient with documented untreated brain metastases.
Systemic responses were observed at multiple dose levels in heavily pre-treated NSCLC patients, characterized by 81% having received prior EGFR exon 20 targeted agents and 86% having CNS metastases at baseline.
At the potential RP2D of 75 mg QD, responses were observed in 2 of 3 EGFR exon 20 patients previously treated with amivantamab, including a confirmed complete response.
Responses were observed at multiple dose levels in HER2 exon 20 patients, including a confirmed partial response with 100% regression of all target lesions.
ORIC-114 demonstrated a favorable safety profile with mainly Grade 1 and 2 treatment related adverse events.
Presented preclinical data for ORIC-114 at ESMO (Free ESMO Whitepaper) Congress 2023 demonstrating potent activity across atypical mutations in EGFR.
The Phase 1b trial of ORIC-114 is ongoing to determine the candidate RP2Ds for dose optimization and the selection of the final RP2D. Expansion cohorts will enroll patients with EGFR exon 20 insertion mutations that are EGFR exon 20 inhibitor-naïve and that have been previously treated with amivantamab, as well as patients with HER2 exon 20 insertion mutations and atypical EGFR mutations. The company expects to report updated Phase 1b data in the first half of 2025.
ORIC-533: a highly potent, orally bioavailable small molecule inhibitor of CD73

Ongoing enrollment in a Phase 1b trial of ORIC-533 in patients with relapsed/refractory multiple myeloma.
The company will report initial safety, PK/PD, and preliminary antitumor activity data at the 65th ASH (Free ASH Whitepaper) Annual Meeting taking place December 9-12, 2023, in San Diego, CA.
ORIC-944: a potent and selective allosteric inhibitor of PRC2

Ongoing enrollment in a Phase 1b trial of ORIC-944 in patients with advanced prostate cancer.
Expect to report initial safety, PK/PD, and preliminary antitumor activity data in the first quarter of 2024.
Third Quarter 2023 Financial Results

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments totaled $256.2 million as of September 30, 2023, which the company expects will be sufficient to fund its current operating plan into late 2025.
R&D Expenses: Research and development (R&D) expenses were $22.4 million for the three months ended September 30, 2023, compared to $14.7 million for the three months ended September 30, 2022, an increase of $7.7 million. For the nine months ended September 30, 2023, R&D expenses were $60.7 million, compared to $45.4 million for the nine months ended September 30, 2022, an increase of $15.3 million. The increases were due to a net increase in external expenses related to the advancement of product candidates and discovery programs, as well as higher personnel costs.

G&A Expenses: General and administrative (G&A) expenses were $6.3 million for the three months ended September 30, 2023, compared to $6.0 million for the three months ended September 30, 2022, an increase of $0.3 million. For the nine months ended September 30, 2023, G&A expenses were $18.7 million, compared to $19.3 million for the nine months ended September 30, 2022, a decrease of $0.6 million. The decrease was primarily due to a decrease in professional fees.

IPR&D Expenses: Acquired in-process research and development (IPR&D) expenses of $5.0 million for the three and nine months ended September 30, 2022, were due to a development milestone payment related to ORIC-114. There were no such expenses for the three and nine months ended September 30, 2023.

On November 6, 2023 OPKO Health, Inc. (NASDAQ: OPK) reported business highlights and financial results for the three and nine months ended September 30, 2023 (Press release, Opko Health, NOV 6, 2023, View Source [SID1234637041]).

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Business highlights from the third quarter and subsequent weeks included the following:

ModeX Therapeutics Inc. (ModeX) was awarded a contract from the Biomedical Advanced Research and Development Authority (BARDA) to develop novel multispecific antibodies against viral infectious disease threats. BARDA awarded a contract to ModeX to advance a platform and specific therapeutic candidates designed to address a range of public health threats in viral infectious diseases. The BARDA contract includes an initial $59 million award for the development, manufacturing and execution of a Phase 1 clinical trial for a next-generation MSTAR multispecific antibody with broad neutralizing activity against known variants of SARS-CoV-2. ModeX may be eligible to receive up to an additional $109 million from BARDA upon achieving milestones to develop multispecific antibodies targeting other viral pathogens, such as influenza.
ModeX advanced its antiviral and immune-oncology product pipeline. ModeX advanced its pipeline of antiviral and immune-oncology programs utilizing its next-generation multispecific antibodies. ModeX’s oncology programs are in the preclinical stage and at least one program is expected to enter the clinic in 2024. ModeX’s collaboration with Merck to develop MDX-2201, its vaccine for Epstein-Barr virus, is advancing. ModeX’s antiviral program is focused on developing multiple indications, including HIV, as well as other potential viral pathogens funded by BARDA.
NGENLA has now been approved in 48 markets including the U.S., Japan, EU Member States, Canada and Australia; sales are underway by Pfizer in over 23 countries including all priority global markets. NGENLA is the first once-weekly product approved for the treatment of pediatric growth hormone deficiency in Japan, Canada, Australia, the United Kingdom, Taiwan, United Arab Emirates and Brazil. OPKO is entitled to gross profit sharing in all global markets based on regional, tiered gross profit for both NGENLA and Genotropin. The U.S. region commenced gross profit sharing in August 2023.
New clinical data on RAYALDEE presented at Kidney Week 2023. OPKO Health presented late-breaking clinical data on RAYALDEE extended-release calcifediol in a poster presentation at the American Society of Nephrology Kidney Week. The data indicate that early, sustained and effective treatment of secondary hyperparathyroidism (SHPT) with RAYALDEE is associated with significantly slower progression of chronic kidney disease (CKD) in pre-dialysis patients. Data presented in an additional poster demonstrated that effective control of SHPT was achieved with RAYALDEE in both randomized clinical trials and in a real-world clinical experience trial.
OPKO Biologics entered into a research collaboration agreement with Entera Bio Ltd. to develop oral peptide tablet formulations for obesity and intestinal malabsorption syndromes. Under the agreement, OPKO will supply its long-acting GLP-2 peptide and certain oxyntomodulin (OXM) analogs for the development of oral tablet formulations using Entera’s proprietary oral delivery technology. Treatment with glucagon-like peptide-2 (GLP-2) analogs has been shown to improve the absorption of nutrients in patients with short bowel syndrome and to reduce parenteral support requirements. OXM is a naturally occurring peptide hormone found in the colon, with glucagon-like peptide-1 (GLP-1) and glucagon dual agonist activity that suppresses appetite and induces weight loss. OPKO has developed several proprietary, modified OXM analogs as potential candidates for treating obesity, including an injectable pegylated peptide that demonstrated significant reductions in weight loss and decreased plasma triglyceride levels in a 420-patient Phase 2b study.
BioReference Health continued executing its plan to improve operational efficiencies and enhance productivity, and is on track to return to profitability. BioReference continued to implement initiatives to reduce costs and rationalize its business in line with current testing volumes. Additionally, BioReference is focused on improving productivity and enhancing innovation of its higher-value specialty testing segments. Other efforts to return this business to profitability include expanding into new market segments, such as providing information for the pharmaceutical market.
Third Quarter Financial Results

Pharmaceuticals: Revenue from products in the third quarter of 2023 increased to $40.7 million from $32.4 million in the third quarter of 2022, driven by higher sales in OPKO’s international operating companies positively impacted by foreign currency exchange fluctuations of $2.9 million, and by an increase in sales of RAYALDEE to $7.3 million from $6.9 million in the prior-year period. Revenue from the transfer of intellectual property was $6.2 million in the third quarter of 2023 compared with $4.5 million in the 2022 period, which included revenue of $4.9 million and $1.4 million, respectively, of gross profit share for NGENLA in Europe and Japan and does not include an estimate from gross profit in the U.S. as our partner has not yet provided details post their launch in August 2023. Total costs and expenses were $72.3 million in the third quarter of 2023, up from $65.2 million in the prior-year period. The increase was mainly from the cost of revenue due to higher sales in OPKO’s international operating companies, higher inventory costs compared with the 2022 third quarter and unfavorable foreign currency exchange fluctuations of $2.2 million. Operating loss was $25.4 million in the third quarter of 2023 compared with $28.3 million in the third quarter of 2022.
Diagnostics: Revenue from services in the third quarter of 2023 was $131.7 million compared with $142.9 million in the prior-year period. Revenue decreased $10.0 million due to lower COVID-19 testing volume and reimbursement. Furthermore, clinical test reimbursement decreased by $6.6 million due to the mix of testing ordered, partially offset by a $5.4 million increase in clinical test volume. Total costs and expenses were $160.8 million in the third quarter of 2023 compared with $192.3 million in the third quarter of 2022, resulting in an operating loss of $29.1 million compared with an operating loss of $49.5 million in the 2022 period, an improvement of 41%. Operating loss improved primarily due to continued cost-reduction initiatives at BioReference as we strive to return to profitability.
Consolidated: Consolidated total revenues for the third quarter of 2023 were $178.6 million compared with $179.7 million for the comparable 2022 period. Operating loss for the third quarter of 2023 was $64.4 million compared with an operating loss of $87.8 million for the 2022 quarter. Net loss for the third quarter of 2023 included a mark-to-market adjustment of $8.3 million compared with $30.6 million in the 2022 period related to the decrease in the share price of GeneDx, resulting in a net loss of $84.5 million, or $0.11 per share, compared with a net loss of $86.1 million, or $0.11 per share, for the 2022 quarter.
Cash and cash equivalents: Cash and cash equivalents were $138.6 million as of September 30, 2023.
Conference Call and Webcast Information

OPKO’s senior management will provide a business update, discuss third quarter financial results, provide financial guidance and answer questions during a conference call and audio webcast today beginning at 4:30 p.m. Eastern time. Participants are encouraged to pre-register for the conference call using this link. Callers who pre-register will receive a unique PIN to gain immediate access to the call and bypass the live operator. Participants may register at any time, including up to and after the call start time. Those unable to pre-register can participate by dialing 833-630-0584 (U.S.) or 412-317-1815 (International). A webcast of the call can also be accessed at OPKO’s Investor Relations page and here.

A telephone replay will be available until November 13, 2023 by dialing 877-344-7529 (U.S.) or 412-317-0088 (International) and providing the passcode 8299382. A webcast replay will be available beginning approximately one hour after the completion of the live conference call here.

On November 6, 2023 Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in genetic testing and precision medicine, reported financial results for its third quarter ended September 30, 2023 (Press release, Myriad Genetics, NOV 6, 2023, View Source [SID1234637040]). The Company also provided an update on its business performance and 2023 financial guidance.

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"For the third quarter and year-to-date 2023, Myriad Genetics generated revenue growth of 14% and 15% over the prior year periods, respectively, excluding prior period collections1. In the third quarter of 2023, we continued to gain share in hereditary cancer testing, reporting a fifth consecutive quarter of volume growth year-over-year, and saw an acceleration in growth in our prenatal testing business, generating 20% year-over-year volume growth, excluding our Sneakpeek Early Gender DNA Test," said Paul J. Diaz, president and CEO, Myriad Genetics. "With industry leading gross margins and diligent cash management, we believe we have demonstrated our commitment to achieving profitability all while growing the business. We also improved our financial flexibility by expanding our credit facility. We remain confident in our ability to achieve our goal of adjusted profitability by the fourth quarter 2023 and sustainable 10%+ annual revenue growth for this full year and beyond."

Financial and Operational Highlights:
•Test volumes of 356,000 in the third quarter of 2023 increased 40% year-over-year, or 18% excluding contributions from the SneakPeek Early Gender DNA Test.
•The following table summarizes year-over-year quarterly testing volume changes in the company’s core product categories:
Three months ended
September 30, 2023 Nine months ended
September 30, 2023 Three months ended
September 30, 2022 Nine months ended
September 30, 2022

Year-over-Year Year-over-Year Year-over-Year Year-over-Year
Product volumes:
Hereditary cancer
18 % 20 % 4 % (6) %
Tumor profiling (1) % 7 % 3 % (4) %
Prenatal 85 % 78 % 0 % (2) %
Pharmacogenomics
19 % 24 % 34 % 40 %
Total 40 % 41 % 12 % 8 %

•Excluding contributions from the SneakPeek Early Gender DNA Test:
◦Prenatal testing volumes in the third quarter 2023 increased 20% year-over-year and was flat sequentially. In the second quarter 2023 prenatal testing volumes increased 12% year-over-year and 1% sequentially.
•The following table summarizes year-over-year quarterly revenue changes in the company’s core businesses by product category:
Three months ended Nine months ended
(in millions)
September 30, 2023 September 30, 2022
% Change
September 30, 2023
September 30, 2022
% Change
Product revenues:
Hereditary cancer
$
86.5
$
70.5 23 %
$
238.9
$
220.6 8 %
Tumor profiling
30.2 30.8 (2) % 103.5 96.9 7 %
Prenatal 39.5 22.1 79 % 111.3 87.3 27 %
Pharmacogenomics
35.7 33.0 8 % 102.9 95.5 8 %
Total $ 191.9 $ 156.4 23 % $ 556.6 $ 500.3 11 %

•Year-over-year revenue growth in the third quarter of 2023 reflects a $7.1 million change of estimate1 in the current quarter versus $(5.3) million change of estimate1 in the third quarter of 2022, excluding these change of estimates1, third quarter 2023 revenue increased 14% year-over-year, and hereditary cancer testing revenue increased 13% year-over-year.
•GAAP gross margins of 70.0% in the third quarter of 2023; adjusted gross margins for the third quarter of 2023 was 70.4%, an increase of 140.0 basis points from the second quarter of 2023.
•GAAP total operating expenses in the third quarter of 2023 were $194.4 million. Adjusted operating expenses in the quarter were $137.3 million.

•GAAP operating loss in the third quarter of 2023 was $60.1 million, which factors in an accrual related to the settlement of the Ravgen litigation of which $5 million was paid on October 31, 2023, $5 million is payable on or before October 31, 2024, and $2.75 million is payable on or before October 31, 2025. An additional $21.25 million is contingent on whether Ravgen is successful in resolving all outstanding patent re-examinations and litigation. If payable, the contingent amount would be payable over a five year period beginning no earlier than 2026. The adjusted operating loss in the quarter was $2.2 million.
•Ended the third quarter of 2023 with $86.3 million in cash, cash equivalents and marketable investment securities and $23.5 million available to draw under the asset-based credit facility, or total liquidity of $109.8 million. In addition, in October 2023, Myriad Genetics exercised its option to increase the maximum principal amount of its asset-based credit facility by $25.0 million to a total of $115.0 million.

Business Performance and Highlights:

Oncology
The Myriad Genetics Oncology business provides hereditary cancer testing, including the MyRisk hereditary cancer test for patients who have cancer. It also provides tumor profiling products such as the myChoice CDx companion diagnostic test, the Prolaris prostate cancer test, Precise Tumor molecular profile test and the EndoPredict breast cancer prognostic test. The Oncology business delivered revenue of $76.6 million in the third quarter of 2023.
•Third quarter hereditary cancer testing revenue and volumes in Oncology grew 21% and 15% year-over-year, respectively.
•Prolaris continued to see healthy demand as third quarter testing revenue and volumes grew 18% and 9% year-over-year, respectively. UnitedHealthcare has recently issued a positive medical policy covering Prolaris in the biopsy setting for all risk groups. This policy will take effect on January 1, 2024.
•Announced a collaboration with Memorial Sloan Kettering Cancer Center (MSK) to study the use of minimal residual disease (MRD) testing in breast cancer. The research project will use Myriad Genetics’ MRD testing platform, a tumor-informed high-definition assay that uses whole-genome sequencing to achieve high sensitivity and specificity for circulating tumor DNA (ctDNA). Myriad Genetics’ MRD test was selected for its anticipated higher sensitivity and specificity than many other ctDNA offerings.
•Integrated Absolute Risk Reduction (ARR) into the Prolaris Prostate Cancer Prognostic Test to help patients and providers make personalized treatment decisions regarding hormone therapy. Prolaris is the only biomarker test to quantify the benefits of adding androgen deprivation therapy (ADT) to radiation therapy (RT)2.

Women’s Health
The Myriad Genetics Women’s Health business serves women of all ancestries by assessing their risk of cancer and offers prenatal testing solutions for those who are pregnant or planning a family. The Women’s Health business delivered revenue of $79.6 million in the third quarter of 2023.
•Third quarter hereditary cancer testing volumes in Women’s Health grew 22% year-over-year, driven by competitive account wins and increased adoption by providers of MyRisk for patients whose family history puts them at a higher risk for cancer.
•Excluding contributions from the SneakPeek Early Gender DNA Test, prenatal testing volumes in the third quarter of 2023 grew 20% year-over-year.
•In collaboration with Onsite Women’s Health, a leading national provider of breast health services, we announced the launch of a new breast cancer risk assessment program to help more women understand their breast cancer risk. This program combines diagnostic imaging and genetic risk assessment utilizing MyRisk with RiskScore and patient education. The program is expected to enable affordable access to genetic testing and deliver personalized insights to better inform clinical decisions for millions of potential patients.
•MyRisk Hereditary Cancer Test with RiskScore now incorporates breast density using Tyrer-Cuzick version 8 (TCv8) to provide patients and providers with a more comprehensive look at their five-year and remaining lifetime risk for breast cancer. MyRisk with RiskScore is the first breast cancer risk model that includes breast density, personal/family clinical history and a polygenic risk score (PRS) based on genetically determined ancestry.
•As of October 2023, Myriad Genetics sold over 1 million SneakPeek Early Gender DNA Tests.
Pharmacogenomics
The Myriad Genetics Pharmacogenomics business consists of the GeneSight test that covers 64 medications commonly prescribed for depression, anxiety, attention deficit hyperactivity disorder, and other psychiatric conditions. GeneSight helps physicians understand how genetic alterations impact patient response to antidepressants and other drugs. In the pharmacogenomics category, the GeneSight test recorded revenue of $35.7 million in the third quarter of 2023.
•In the third quarter, Myriad Genetics added approximately 4,000 clinicians who ordered GeneSight for the first time.
•Enhanced GeneSight report will now include information on how a patient’s smoking status may impact their body’s metabolism of certain medications.

•Presented positive preliminary results from Phase 1 of a multi-phase study designed to better understand GeneSight’s ability to improve clinical outcomes and reduce healthcare costs. Based on data from over 20,000 patients in the Optum Labs Data Warehouse, in the first 180 days post GeneSight testing, total hospitalizations decreased by more than 25% and psychiatric hospitalizations decreased by more than 35%. Additional data and detail from this study is expected to be published in 2024.
•Building on a 2020 meta-analysis of the clinical utility of the GeneSight test, which included four prospective, controlled studies and 1,556 unique patients, Myriad Genetics has incorporated additional published studies to further measure the utility of combinatorial pharmacogenomics testing for the treatment of major depressive disorder (MDD). This updated meta-analysis continues to show that access to GeneSight improved MDD response and remission rates.

On November 6, 2023 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a growing pipeline, including Phase 2 clinical programs, for hard-to-treat tumors and viruses, reported the presentation of preliminary efficacy findings from the Phase 2 portion of the Company’s ongoing U.S. Phase 1B/2 clinical trial evaluating Annamycin for the treatment of soft tissue sarcoma lung metastases (MB107) (Press release, Moleculin, NOV 6, 2023, View Source [SID1234637039]).

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The abstract titled, "A Phase 1b/2 Study of Liposomal Annamycin (ANN) in Subjects with Previously Treated Soft-Tissue Sarcomas (STS) with Pulmonary Metastases," was presented by Brian Andrew Van Tine, MD, PhD, Professor of Medicine, Washington University School of Medicine in a poster presentation at the 2023 CTOS Annual Meeting being held November 1-4, 2023 in Dublin, Ireland.

"Our growing body of preliminary data demonstrated by Annamycin in the treatment of patients with STS lung mets continues to be encouraging and bolsters our confidence in its potential to be a meaningful option for patients," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin. "While still preliminary, the rates of the median progression free response and the trend being established for overall survival despite the patients in this study having received multiple prior chemotherapy regimens continues to exceed our expectations. We look forward to further data readouts from this trial and understanding the full potential of Annamycin for the treatment of STS lung mets."

19 subjects were enrolled in the Phase 1B portion of the MB107 study. The median number of cycles administered was 2. There were no significant safety concerns or unexpected serious adverse events (SAEs) up to the 390 mg/m2 dose. The recommended Phase 2 dose (RP2D) was defined as 330 mg/m2. The most frequently reported adverse events (AEs) related to Annamycin were in the system organ class of Investigations (decreased platelet counts). There was no evidence of cardiotoxicity as measured by ejection fraction, strain analyses, ECGs, and cardiac biomarkers including Troponin-I and T. In Phase 2, 14 subjects (median # of prior therapies = 3) received at least 2 cycles of Annamycin at 330 mg/m2.

Of the 14 subjects enrolled in the Phase 2 portion of the trial, 9 (64%) showed stable disease (SD) through 2 cycles, 5 (36%) of whom continued to show SD through 4 cycles, and 2 (14%) showed SD through 6 cycles. Of these 2, one subject maintained SD through the end of 6 cycles prior to progressing ~6.2 months after initiating treatment with Annamycin. The other subject maintained SD through 8 cycles prior to progressing ~6.9 months after initiating treatment with Annamycin. 3 subjects continue to be followed for progression free survival (PFS), and 12 of 14 subjects in the Phase 2 efficacy population continue to be followed for overall survival (OS).

Annamycin currently has Fast Track Status and Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of soft tissue sarcoma, in addition to Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia. For more information about the U.S. Phase 1B/2 clinical trial evaluating Annamycin for the treatment of soft tissue sarcoma lung metastases (MB107) visit clinicaltrials.gov and reference identified NCT04887298.

Study Design

In Phase 2, Annamycin was administered as an intravenous (IV) infusion over 2 hours on Day 1, followed by 20 days off therapy (1 cycle = 21 days). Subjects visit the study site every 21 days (±3 days) at which time safety monitoring – including for adverse events (AEs), as well as a physical examination, laboratory evaluations (clinical chemistry, complete blood count), vital signs, weight measurements, Eastern Cooperative Oncology Group (ECOG) performance status, and electrocardiograms (ECGs) – are performed, followed by an IV infusion of study drug. Cardiac function is followed by echocardiogram (ECHO) scans at screening, at the end of the first two cycles and then following every other cycle thereafter, at the End of Treatment visit, and if feasible, during follow up at 6 months (±1 month) and 1 year (±1 month) after study drug discontinuation. As long as the Investigator considers that the benefits of treatment with Annamycin continue to outweigh the risks, treatment will continue every 21 days until tumor progression is observed or unacceptable toxicity occurs.

Tumor response is monitored every 6 weeks (±1 week) from Cycle 1 Day 1 during treatment, at the End of Treatment visit, and then every 3 months (±1 month) until disease progression using RECIST 1.1 criteria. Those subjects who leave the study after a maximum response is achieved and who do not start another therapy will be followed every 3 months (±1 month) for progression-free survival (PFS). If a subject receives further therapy after discontinuing from the study, they will be followed only for overall survival (OS) and if feasible, follow-up ECHO scans at 6 months (±1 month) and 1 year (±1 month) will be conducted after study drug discontinuation.

About Annamycin

Annamycin is the Company’s next-generation anthracycline that has been shown in animal models to accumulate in the lungs at up to 30-fold the level of doxorubicin. Importantly, Annamycin has also demonstrated a lack of cardiotoxicity in multiple early-stage human clinical trials, including ongoing trials for the treatment of acute myeloid leukemia (AML) and STS lung metastases. For that reason, although additional data will be necessary, the Company believes Annamycin may not face the same usage limitations imposed on doxorubicin, one of the most common currently approved anthracyclines. Annamycin is currently in development for the treatment of AML and STS lung metastases and the Company believes the drug may have the potential to treat additional indications.

On November 6, 2023 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a commercial stage biotechnology company, reported financial results for the third quarter 2023 along with recent pipeline and corporate updates (Press release, Mirati, NOV 6, 2023, View Source [SID1234637038]).

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"We are pleased to share the significant progress made during the third quarter of 2023, highlighted by the advancement of our robust pipeline of targeted oncology programs and continued launch execution of KRAZATI," said Charles Baum, M.D., Ph.D., CEO, president and founder, Mirati Therapeutics, Inc. "As we shared last month, we believe our pending acquisition by Bristol Myers Squibb will support the realization of the full potential of our therapies and enable the promise of a life beyond cancer. We look forward to continuing our work to improve the lives of people with cancer through Mirati discovered and developed therapeutics."

Pipeline Updates

Adagrasib (Potent and selective KRASG12C inhibitor)

•In November, the Company announced the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) granted conditional marketing authorization approval for KRAZATI (adagrasib) as a monotherapy indicated for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with KRASG12C mutation and have progressive disease after prior therapy with, or intolerance to, platinum-based chemotherapy and/or anti-PD-1/PD-L1 immunotherapy.

•In October, the Company shared updated results from the KRYSTAL-7 Phase 2 study evaluating adagrasib combined with pembrolizumab in patients with first-line NSCLC with a KRASG12C mutation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (ESMO) (Free ESMO Whitepaper) 2023.

•In September, the Company shared two-year follow-up data from a pooled analysis of the Phase 1/1b Cohort and Phase 2 Cohort A for the KRYSTAL-1 study evaluating adagrasib in NSCLC patients harboring a KRASG12C mutation at 2023 World Conference on Lung Cancer (WCLC).

•In September, the Company shared that adagrasib has been included in the National Comprehensive Cancer Network (NCCN) Guidelines for Colon and Rectal Cancer for patients harboring a KRASG12C mutation.

•The Company completed enrollment in KRYSTAL-10, a Phase 3 registrational clinical study in second-line colorectal cancer patients with a KRASG12C mutation, evaluating the combination of adagrasib plus cetuximab versus chemotherapy.

•The Company continues to enroll in KRYSTAL-12, a Phase 3 clinical study of adagrasib versus docetaxel in second line NSCLC patients.

•Re-examination by the European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) of the Conditional Marketing Authorisation Application (MAA) for KRAZATI (adagrasib) for the treatment of patients with KRASG12C-mutated advanced NSCLC is ongoing.

MRTX1719 (MTA cooperative PRMT5 inhibitor)
1

•In August, the Company shared initial clinical data in patients with MTAP-deleted cancers. The Company continues to enroll patients in the Phase 1/2 clinical study.

MRTX1133 (Potent and selective KRASG12D inhibitor)

•The Company continues to enroll patients in the Phase 1/2 clinical study.

MRTX0902 (Potent SOS1 inhibitor)

•The Company continues to advance the Phase 1/2 clinical study evaluating the combination of MRTX0902 plus adagrasib.

Recent Corporate Updates
•In October, the Company and Bristol Myers Squibb announced their entry into a merger agreement under which Bristol Myers Squibb has agreed to acquire Mirati for $58.00 per share in cash, for a total equity value of $4.8 billion. Mirati stockholders will also receive one non-tradeable Contingent Value Right (CVR) for each Mirati share held, potentially worth $12.00 per share in cash, representing an additional $1.0 billion of value opportunity. The transaction is anticipated to close by the first half of 2024, subject to fulfillment of customary closing conditions, including approval of the Company’s stockholders and receipt of the required regulatory approvals.

•In August, the Company executed an underwritten public offering.

Third Quarter Financial Results

•Cash, cash equivalents and short-term investments of approximately $976.4 million as of September 30, 2023, including proceeds from an August 2023 public offering of our common stock that generated net proceeds of $332.5 million. Excluding the August 2023 financing, net decrease in cash, cash equivalents and short-term investments for the third quarter of 2023 was $135.5 million.

•Net KRAZATI product revenue for the three and nine months ended September 30, 2023 was $16.4 million and $36.1 million, respectively. Net product revenue during the three and nine months ended September 30, 2023 is comprised of $15.1 million and $33.1 million, respectively, of commercial sales and $1.3 million and $3.0 million, respectively, of sales to a third-party commercial customer for its clinical trials. There was no product revenue for the same periods in 2022.

•License and collaboration revenue for the three and nine months ended September 30, 2023 was zero and $1.2 million, respectively, related to clinical supply revenue earned under the agreement with Zai Lab. License and collaboration revenue for the same periods in 2022 was $5.4 million and $11.5 million, respectively, related to milestone payments from Zai Lab and clinical supply revenue earned under the agreement with Zai Lab.

•Cost of product revenue for the three and nine months ended September 30, 2023 was $1.7 million and $3.8 million, respectively, of which $1.4 million and $3.0 million, respectively, related to product manufacturing and distribution costs, and royalties incurred on net sales of KRAZATI. There was no cost of product revenue for the same periods in 2022.

•Research and development expenses for the three and nine months ended September 30, 2023 were $114.8 million and $365.6 million, respectively, compared to $131.1 million and $390.4 million for the same periods in 2022, respectively. The decrease was primarily driven by a reduction in clinical development costs for sitravatinib as the Company is no longer pursuing further clinical development, and a decrease in share-based compensation, partially offset by increases in costs for earlier stage clinical development programs such as MRTX1133.

•Selling, general and administrative expenses for the three and nine months ended September 30, 2023 were $72.0 million and $221.0 million, respectively, compared to $60.8 million and $169.0 million, respectively for the same periods in 2022. The increases were primarily due to an increase in headcount-related costs, including share-based compensation, and commercial-related costs to support the marketing and sales of KRAZATI.

•Net loss for the three months ended September 30, 2023 was $161.9 million, or $2.49 per share basic and diluted, compared to a net loss of $173.6 million, or $3.09 per share basic and diluted for the same period in 2022. Net loss for the nine months ended September 30, 2023 was $523.4 million, or $8.66 per share basic and diluted, compared to a net loss of $538.4 million, or $9.66 per share basic and diluted for the same period in 2022.