On November 14, 2022 AstraZeneca and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of LYNPARZA in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) in whom chemotherapy is not clinically indicated (Press release, AstraZeneca, NOV 14, 2022, View Source [SID1234624003]).

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The CHMP based its positive opinion on results from the Phase 3 PROpel trial presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium and later published in NEJM Evidence.

These results showed LYNPARZA in combination with abiraterone and prednisone or prednisolone reduced the risk of disease progression or death by 34% (HR=0.66 [95% CI, 0.54-0.81]; p<0.0001) versus placebo plus abiraterone and prednisone or prednisolone. Median radiographic progression-free survival (rPFS) was 24.8 months for the LYNPARZA plus abiraterone arm versus 16.6 months for the placebo plus abiraterone arm, with or without homologous recombination repair (HRR) gene mutations.

The safety and tolerability of LYNPARZA in combination with abiraterone and prednisone or prednisolone was in line with that observed in prior clinical trials and the known profiles of the individual medicines. The most common adverse events (AEs) (≥20%) were anemia (46%), fatigue (37%) and nausea (28%). Grade ≥3 AEs were anemia (15%), hypertension (4%), urinary tract infection (2%), fatigue (2%), decreased appetite (1%), vomiting (1%), back pain (1%), diarrhea (1%) and nausea (0.3%). Approximately 14% of patients who received LYNPARZA in combination with abiraterone and prednisone or prednisolone discontinued treatment due to an AE.

Prostate cancer is the most commonly diagnosed cancer in men in Europe, with an estimated 473,000 cases and 108,000 deaths in 2020. Approximately 10-20% of patients with advanced prostate cancer are estimated to develop castration-resistant prostate cancer (CRPC) within five years, and at least 84% of these men will develop metastases at the time of CRPC diagnosis. Patients with advanced prostate cancer have a particularly poor prognosis, and the five-year survival rate remains low.

Noel Clarke, urological surgeon and professor of urological oncology at the Christie/Salford Royal Hospitals and University of Manchester and the PROpel trial joint senior investigator, said, "Patients with mCRPC in the European Union have limited treatment options. This form of advanced prostate cancer has a poor prognosis, and treatment decisions after initial diagnosis are critical. If approved in the European Union for prostate cancer of this type, olaparib in combination with abiraterone will provide a much-needed new treatment option for the many men with this condition."

Susan Galbraith, executive vice president, oncology R&D, AstraZeneca, said, "With the incidence and mortality of prostate cancer set to double in the coming decades, it is more important than ever that we bring new treatment options to suitable patients at the earliest possible moment in their care. If approved, LYNPARZA in combination with abiraterone and prednisone or prednisolone will represent the first combination of a PARP inhibitor and a new hormonal agent available to patients in the European Union."

Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, said, "While prostate cancer has seen many advances in care in recent decades, for those with mCRPC, new treatment options are urgently needed. We are fully committed to bringing LYNPARZA in combination with abiraterone and prednisone or prednisolone to suitable patients in Europe as quickly as possible."

LYNPARZA in combination with abiraterone and prednisone or prednisolone is undergoing priority review in the U.S. for the treatment of adult patients with mCRPC based on results from the Phase 3 PROpel trial, with a decision expected in Q4 2022.

LYNPARZA monotherapy is approved in the U.S. based on results from the Phase 3 PROfound trial for patients with HRR gene-mutated mCRPC (BRCA-mutated and other HRR gene mutations) who have progressed following prior treatment with enzalutamide or abiraterone; and in the European Union, Japan and China for patients with BRCA-mutated mCRPC who have progressed following prior therapy that included a new hormonal agent (NHA).

About PROpel
PROpel (ClinicalTrials.gov, NCT03732820) is a randomized, double-blind Phase 3 trial testing the efficacy, safety and tolerability of LYNPARZA versus placebo when given in addition to abiraterone and prednisone or prednisolone in patients with mCRPC who had not received prior chemotherapy or NHAs in the mCRPC setting. The primary endpoint is rPFS, and secondary endpoints include overall survival, time to secondary progression or death and time to first subsequent therapy.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS/AML was 2 years (range: <6 months to >10 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in 0.8% of patients exposed to LYNPARZA monotherapy, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

Females
Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

Males
Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

Venous Thromboembolic Events: Including pulmonary embolism, occurred in 7% of patients with metastatic castration-resistant prostate cancer who received LYNPARZA plus androgen deprivation therapy (ADT) compared to 3.1% of patients receiving enzalutamide or abiraterone plus ADT in the PROfound study. Patients receiving LYNPARZA and ADT had a 6% incidence of pulmonary embolism compared to 0.8% of patients treated with ADT plus either enzalutamide or abiraterone. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated.

ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary tract infection (13%), thrombocytopenia (11%), and stomatitis (11%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).

ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab
Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab compared to a ≥5% frequency for placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%) and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%) and headache (14%).

In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%) and decrease in platelets (35%).

ADVERSE REACTIONS—Maintenance Recurrent Ovarian Cancer
Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), decreased appetite (21%) and dyspepsia (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

ADVERSE REACTIONS—Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: nausea (57%), fatigue (including asthenia) (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%), and stomatitis (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: decrease in lymphocytes (77%), increase in mean corpuscular volume (67%), decrease in hemoglobin (65%), decrease in leukocytes (64%), and decrease in absolute neutrophil count (39%).

ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer
Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).

Most common laboratory abnormalities (Grades 1-4) in >25% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).

ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic Pancreatic Adenocarcinoma
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%).

ADVERSE REACTIONS—HRR Gene-mutated Metastatic Castration Resistant Prostate Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA for PROfound were: anemia (46%), fatigue (including asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and dyspnea (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).

DRUG INTERACTIONS
Anticancer Agents: Clinical studies of LYNPARZA with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

CYP3A Inhibitors: Avoid coadministration of strong or moderate CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid coadministration of strong or moderate CYP3A inducers when using LYNPARZA.

USE IN SPECIFIC POPULATIONS
Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).

Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

INDICATIONS for LYNPARZA in the United States
LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for:

First-Line Maintenance BRCAm Advanced Ovarian Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance HRD-Positive Advanced Ovarian Cancer in Combination with Bevacizumab
In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

a deleterious or suspected deleterious BRCA mutation and/or
genomic instability
Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance Recurrent Ovarian Cancer
For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.

Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer
For the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

gBRCAm HER2-Negative Metastatic Breast Cancer
For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, who have been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

HRR Gene-mutated Metastatic Castration Resistant Prostate Cancer
For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Please see complete Prescribing Information, including Medication Guide.

About LYNPARZA (olaparib)
LYNPARZA is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. LYNPARZA is being tested in a range of tumor types with defects and dependencies in the DDR.

LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad and advanced clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types.

About metastatic castration-resistant prostate cancer
Prostate cancer is the second most common cancer in male patients globally and is associated with a significant mortality rate. Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone. In patients with mCRPC, their prostate cancer grows and spreads to other parts of the body, despite the use of androgen-deprivation therapy to block the action of male sex hormones. Approximately 10-20% of patients with advanced prostate cancer will develop CRPC within five years, and at least 84% of these patients will have metastases at the time of CRPC diagnosis. Of patients with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.

About the AstraZeneca and Merck strategic oncology collaboration
In July 2017, AstraZeneca and Merck, known as MSD outside of the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize certain oncology products including LYNPARZA, the world’s first PARP inhibitor, for multiple cancer types. Working together, the companies will develop these products in combination with other potential new medicines and as monotherapies. Independently, the companies will develop these oncology products in combination with their respective PD-L1 and PD-1 medicines.

On November 14, 2022 MEI Pharma, Inc. (Nasdaq: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported results for the quarter ended September 30, 2022, and highlighted recent corporate events (Press release, MEI Pharma, NOV 14, 2022, View Source [SID1234624002]).

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"As we move through fiscal year 2023 and continue to assess FDA concerns regarding the risk benefit analysis of marketed PI3Kδ inhibitors to treat indolent lymphomas, as well as the impact of these concerns and other global factors on our Phase 3 COASTAL study, we also look forward to reporting advances across our clinical development pipeline. This includes reporting updated data from multiple zandelisib studies at the ASH (Free ASH Whitepaper) annual meeting in December, and also reporting advances in our other development programs, including initiation of a trial evaluating voruciclib’s potential to synergize with venetoclax in patients with AML, and a trial evaluating the combination of ME-344 plus bevacizumab in patients with relapsed and refractory colorectal cancer," said Daniel P. Gold, Ph.D., president and chief executive officer of MEI Pharma. "We remain well capitalized with $138 million to advance our pipeline and continue operations for approximately two years."

First Quarter Fiscal Year 2023 Recent Developments and Financial Highlights

Earlier in November, MEI Pharma and Kyowa Kirin announced the acceptance of three abstracts reporting data for zandelisib, an investigational phosphatidylinositol 3-kinase delta inhibitor in clinical development for the treatment of B-cell malignancies, to be presented at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) 2022 annual meeting to be held December 10-13, 2022.
In September, we announced that Christine A. White, M.D. will be retiring as chair of the board. She will be replaced by board member Charles V. Baltic. This will be effective as of the Company’s fiscal 2023 annual meeting of shareholders. Additionally, in November, Cheryl L. Cohen also informed the Company that she will not stand for election to the board at the Company’s annual meeting of shareholders.
In July, MEI Pharma and Kyowa Kirin announced publication in The Lancet Oncology of data from Phase 1b clinical study of zandelisib in patients with relapsed or refractory B-cell malignancy.
Expected Drug Candidate Pipeline Developments

Zandelisib – Oral PI3K delta inhibitor for the treatment of various B-cell malignancies

Report new zandelisib data at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2022, including a presentation of updated data from the follicular lymphoma cohort in the Phase 2 TIDAL study and a presentation of data from the Phase 1b study cohort evaluating zandelisib plus Brukinsa (zanubrutinib) to treat indolent B-cell malignancies.
Dose the first patient in the Phase 2 CORAL study evaluating zandelisib plus Venclexta (venetoclax) and rituximab in patients with chronic lymphocytic leukemia by year-end 2022.
Voruciclib – Oral CDK9 inhibitor for the treatment of B-cell malignancies and acute myeloid leukemia

Dose the first patient cohort of voruciclib in combination with Venclexta (venetoclax) in patients with acute myeloid leukemia by year-end 2022 in the Phase 1 study.
ME-344 – Tumor selective mitochondrial inhibitor

Initiate a Phase 1b study evaluating ME-344 plus Avastin (bevacizumab) in relapsed colorectal cancer patients in the first half of calendar year 2023.
First Quarter Fiscal Year 2023 Financial Results

As of September 30, 2022, MEI had $138.4 million in cash, cash equivalents, and short-term investments with no outstanding debt.
For the quarter ended September 30, 2022, cash used in operations was $14.8 million, compared to $7.7 million used in operations for the quarter ended September 30, 2021. The increase in cash used in operations is due to the favorable impact of a $10.0 million milestone payment received from Kyowa Kirin in the comparable quarter in 2021 with no corresponding payment in 2022 and other changes in working capital balances.
Research and development expenses were $19.5 million for the quarter ended September 30, 2022, compared to $20.0 million for the quarter ended September 30, 2021. The decrease was primarily related to costs to support ongoing zandelisib and voruciclib studies.
General and administrative expenses were $7.5 million for the quarter ended September 30, 2022, compared to $7.9 million for the quarter ended September 30, 2021. The decrease primarily relates to lower personnel costs, professional services and general corporate expenses.
MEI recognized revenue of $8.7 million for the quarter ended September 30, 2022, compared to $7.8 million for the quarter ended September 30, 2021. The increase in recognized revenue relates to progress towards completion of our performance obligations, offset by decreased reimbursement of expenses under the license agreement with Kyowa Kirin.
Net loss was $16.6 million, or $0.12 per share, for the quarter ended September 30, 2022, compared to net loss of $17.5 million, or $0.16 per share for the quarter ended September 30, 2021. The Company had 133,260,865 shares of common stock outstanding as of September 30, 2022, compared with 112,678,498 shares as of September 30, 2021.
The adjusted net loss (a non-GAAP measure) for the quarter ended September 30, 2022, excluding non-cash expenses related to changes in the fair value of the warrants, was $17.7 million, compared to an adjusted net loss of $20.1 million for the quarter ended September 30, 2021.

On November 14, 2022 Leap Therapeutics, Inc. (Nasdaq: LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported financial results for the third quarter ended September 30, 2022 (Press release, Leap Therapeutics, NOV 14, 2022, View Source [SID1234624001]).

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Leap Highlights :
Presented clinical data from Part A of the DisTinGuish study of DKN-01 plus BeiGene’s tislelizumab in gastroesophageal adenocarcinoma (GEA) cancer patients, and the Phase 2 WAKING study of DKN-01 plus Tecentriq in oesophagogastric adenocarcinoma (OGA), at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress

Presented clinical data from Part B of the DisTinGuish study of DKN-01 plus tislelizumab in GEA cancer patients whose tumors express high levels of DKK1 (DKK1-high), and preclinical data supporting further evaluation of DNK-01 in colorectal cancer (CRC), at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting

Enrolled first patient into Part C of the DisTinGuish study, the randomized controlled trial of DKN-01 plus tislelizumab and chemotherapy in first-line G/GEJ patients

Enrolled first patient into the Phase 2 DeFianCe study of DKN-01 in second-line CRC patients
"This past quarter saw incredible progress across our DKN-01 program as we continue to focus on execution in our clinical, preclinical, biomarker, and manufacturing activities, and advance into the next stages of development," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "Results from Parts A and B of the DisTinGuish trial have been compelling with updated data presented at both ESMO (Free ESMO Whitepaper) and SITC (Free SITC Whitepaper). We were also delighted to announce the enrollment of the first patients into both Part C of the DisTinGuish gastric cancer study and the newly-initiated DeFianCe colorectal cancer trial, as we explore the broad therapeutic potential of DKN-01."

DKN-01 Development Update
DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein. DKK1 modulates the Wnt/Beta-catenin and PI3kinase/AKT signaling pathways, which play an important role in tumor cell signaling and in mediating an immuno-suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating natural killer (NK) cell ligands on tumor cells.

Updated Clinical Data from Part A of DisTinGuish Study of DKN-01 Plus Tislelizumab in First-Line Patients with Advanced GEA at the ESMO (Free ESMO Whitepaper) Congress. The DisTinGuish study (NCT04363801) is a Phase 2 study of DKN-01 in combination with tislelizumab and standard of care (SOC) chemotherapy in patients with inoperable, locally advanced GEA.
Overall median progression-free survival (PFS) was 11.3 months, exceeding benchmark results in unselected patients and in all four important biomarker-directed subgroups (DKK1-high, DKK1-low, PD-L1-low, and PD-L-1-high).
Median overall survival was not yet reached.
Overall response rate (ORR) was high and durable in unselected and aggressive subgroups (DKK1-high and PD-L1-low); 68% ORR in modified intent-to-treat (mITT) population overall (1 complete response, 14 partial responses).
DKN-01 and tislelizumab plus CAPOX was well tolerated in first-line treatment for advanced GEA patients, with a safety profile consistent with previous reports.

New Clinical Data from WAKING Study of DKN-01 Plus Tecentriq at the ESMO (Free ESMO Whitepaper) Congress. The WaKING study (NCT04166721) is an investigator-sponsored study of DKN-01 in combination with atezolizumab, Roche’s anti-PD-L1 antibody, in patients with microsatellite stable esophago gastric cancer who have progressed following chemotherapy. This study is being sponsored by The Royal Marsden Hospital in the United Kingdom and being funded by Roche as part of its imCORE network.

Updated Data from Part B of DisTinGuish Study of DKN-01 Plus Tislelizumab in Second-Line Patients with Advanced GEA Cancer Whose Tumors Exress High Levels of DKK1-High at the SITC (Free SITC Whitepaper) Annual Meeting.
DKN-01 and tislelizumab were well tolerated at both 300mg and 600mg DKN-01 doses with no Grade 5 treatment-emergent AEs (TEAE) and no TEAEs leading to study drug discontinuation or dose reduction
In evaluable anti-PD-1/PD-L1 naïve mITT population (n=43), 27% ORR and 43% disease control rate (DCR), exceeding the benchmark studies for anti-PD-1 monotherapy
In DKK1-high/PD-L1-high CPS ≥ 10 patients: 55% ORR, 73% DCR, and 7.7 months PFS
In DKK1-high/PD-L1-negative CPS < 1 patients: 27% ORR

New Preclinical Data in Colorectal Cancer (CRC) Models at the SITC (Free SITC Whitepaper) Annual Meeting.
DKN-01 additive activity with 5-fluorouracil (5FU) and can overcome 5FU-resistance in two xenograft models, resulting in tumor regressions. 5FU-resistant models are reflective of a second-line CRC population currently being recruited in the DeFianCe study.
Treatment with DKN-01 as monotherapy or in combination with anti-PD-1 resulted in tumor regression in a CT26 synergenic CRC model.

Leap Announced First Patient Enrolled in Part C of Phase 2 DisTinGuish Study of DKN-01 in Combination with Tislelizumab and Chemotherapy Compared to a Tislelizumab and Chemotherapy Control Arm, in Patients with G/GEJ. The DisTinGuish study (NCT04363801) is a Phase 2 study of DKN-01 in combination with tislelizumab and standard of care (SOC) chemotherapy in patients with inoperable, locally advanced, G/GEJ adenocarcinoma. Part C of the DisTinGuish study will enroll approximately 160 first-line, HER2-negative patients who have had no prior therapy for unresectable locally advanced or metastatic G/GEJ adenocarcinoma.

Leap Announced First Patient Enrolled in DeFianCe Study of DKN-01 in Combination with Standard of Care Bevacizumab and in Chemotherapy in Second-Line Patients for the Treatment of CRC. The DeFianCe study (NCT05480306) is a Phase 2 study of DKN-01 in combination with bevacizumab and SOC chemotherapy in patients with advanced CRC who have received one prior systemic therapy. The study is designed with an initial 20 patient cohort and to then expand into a 130 patient randomized controlled trial against bevacizumab and SOC chemotherapy.
Selected Third Quarter 2022 Financial Results
Net Loss was $15.1 million for the third quarter 2022, compared to $11.1 million for the three months ended September 30, 2021.

Research and development expenses were $12.1 million for the three months ended September 30, 2022, compared to $10.1 million for the three months ended September 30, 2021. The increase of $2.0 million in research and development expenses was due to an increase of $1.4 million in clinical trial costs due to patient enrollment and the duration of patients on study, an increase of $0.4 million in payroll and other related expenses due to increased headcount, and an increase of $0.2 million in stock-based compensation expense.

General and administrative expenses were $3.2 million for the three months ended September 30, 2022, compared to $2.4 million for the three months ended September 30, 2021. The increase of $0.8 million in general and administrative expenses were due to an increase of $0.5 million in professional fees due to higher recruiting costs and an increase of $0.2 million in payroll and other related expenses due to an increase in headcount.

Cash and cash equivalents totaled $78.3 million at September 30, 2022. Additionally, short-term research and development incentive receivable totaled $1.3 million.

On November 14, 2022 Instil Bio, Inc. ("Instil") (NASDAQ: TIL), a clinical-stage biopharmaceutical company focused on developing tumor infiltrating lymphocyte, or TIL, therapies for the treatment of patients with cancer, reported its third quarter 2022 financial results and provided a corporate update (Press release, Instil Bio, NOV 14, 2022, View Source [SID1234623999]).

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Third Quarter 2022 Highlights and Anticipated Milestones:

DELTA-1 manufacturing and regulatory update: As previously announced, enrollment in DELTA-1 was voluntarily paused following the observation of decreased rates of successful manufacturing of ITIL-168. Our ongoing investigation of the manufacturing failures identified a central source of contamination in the cell media. In conjunction with this pause, we are also evaluating opportunities to increase the robustness of our manufacturing process. In addition, in October 2022, we notified the FDA and other regulatory agencies that an unplanned review of the data for the initial patients that had been dosed with ITIL-168 in the DELTA-1 trial was conducted in order to review risk-benefit. This review was inconclusive because the response data were not mature. Subsequently, the Data Safety Monitoring Board’s prespecified review found no safety concerns. We plan to discuss next steps for the DELTA-1 trial with the FDA and other regulatory agencies, and after such discussions, or as a result of our ongoing investigation of our manufacturing process, we may be required to modify, delay or restart our ITIL-168 clinical development program. We plan to provide an update on our ITIL-168 clinical development program in the first quarter of 2023.

DELTA-2 clinical update: The Company is deferring enrollment in the DELTA-2 study to focus resources toward higher-priority clinical programs.

First patient dosed in Phase 1 dose escalation study of ITIL-306, Instil’s first CoStAR-TIL: Instil recently announced dosing of the first patient with non-small cell lung cancer in the Phase 1 dose escalation study of ITIL-306 for the treatment of multiple solid tumors. The ITIL-306 product contained the target dose of approximately 1 billion CoStAR-TILs in addition to unmodified TILs. The CoStAR platform introduces a genetic modification which is designed to enhance the activity of TILs within the tumor microenvironment. The Phase 1 trial of ITIL-306 excludes the high-dose interleukin-2 regimen after ITIL-306 infusion. The Company remains committed to the CoStAR platform and expects to report initial clinical data from the trial in 2023.

Appointment of Head of Research and Development: Instil announced the appointment of Robert Hawkins, M.B.B.S., Ph.D., as Head of Research and Development. Dr. Hawkins is a world-renowned oncologist and biotechnology innovator, with a focus on development of novel cell and gene therapies. Dr. Hawkins was the founder and CEO of Immetacyte Ltd., a cell therapy company spun out of the University of Manchester where Dr. Hawkins served as Professor of Medical Oncology. Immetacyte Ltd. generated the foundational TIL technology and clinical data on which Instil was founded.

Resignation of Chief Medical Officer: Instil announced that, pursuant to a separation agreement, Zachary Roberts, M.D., Ph.D., Chief Medical Officer of the Company, has resigned effective November 11, 2022 to pursue other opportunities. The company appreciates Dr. Roberts’ contributions and wishes him the best in his future endeavors.

Company confirms cash-runway into 2025 with anticipated sale-leaseback transaction of its Tarzana manufacturing facility
Third Quarter 2022 Financial and Operating Results:

As of September 30, 2022, we had $303.3 million in total cash and cash equivalents and marketable securities, comprised of $41.1 million in cash and cash equivalents and $262.2 million in marketable securities, compared to $454.1 million in total cash and cash equivalents and marketable securities, comprised of $37.6 million in cash and cash equivalents and $416.5 million in marketable securities as of December 31, 2021. The Company expects that its cash, cash equivalents and marketable securities as of September 30, 2022 will enable it to fund its operating plan into 2025 upon completion of the anticipated sale-leaseback of its Tarzana, CA manufacturing site.

Research and development expenses were $39.7 million and $120.3 million for the three and nine months ended September 30, 2022, respectively, compared to $29.1 million and $64.7 million for the three and nine months ended September 30, 2021, respectively.

General and administrative expenses were $17.0 million and $49.3 million for the three and nine months ended September 30, 2022, respectively, compared to $14.0 million and $37.1 million for the three and nine months ended September 30, 2021, respectively.

On November 14, 2022 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported its revenues and cash position for the first nine months of 2022 (Press release, Innate Pharma, NOV 14, 2022, View Source [SID1234623998]).

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"Innate’s strong financial position, innovative science and strategic collaborations enable us to progress a focused pipeline of antibodies, including several potentially first-in-class clinical and preclinical candidates, in cancers with high unmet medical need." said Mondher Mahjoubi, Chief Executive Officer of Innate Pharma. "We are pleased to see that lacutamab continues to show clinical activity in mycosis fungoides. We look forward to sharing data from the Phase 2 TELLOMAK trial for lacutamab in Sézary syndrome at ASH (Free ASH Whitepaper), as well as shining the spotlight on our proprietary ANKET platform, which demonstrates an important role in activating an anti-tumor response. Our third strategic pillar continues to advance, as part of our collaboration with AstraZeneca the PACIFIC-9 Phase 3 study of monalizumab in the early non-small cell lung cancer setting."

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Webcast and conference call will be held today at 2:00pm CET (8:00am ET).
The live webcast will be available at the following link:
View Source

Participants may also join via telephone by registering in advance of the event at: View Source Upon registration, participants will be provided with dial-in numbers, a direct event passcode and a unique registrant ID that they may use 10 minutes prior to the event start to access the call.

This information can also be found on the Investors section of the Innate Pharma website, www.innate-pharma.com. A replay of the webcast will be available on the Company website for 90 days following the event.

Click here to download the Presentation.

Pipeline highlights:
Lacutamab (anti-KIR3DL2 antibody):
Preliminary results from the Phase 2 TELLOMAK study were presented at the EORTC-CLTG (European Organisation for Research and Treatment of Cancer – Cutaneous Lymphoma Tumours Group) 2022 meeting on 23 September, confirming clinical activity and favorable safety profile of lacutamab in patients with mycosis fungoides who express KIR3DL2 and who were previously treated with at least two lines of systemic therapy. Results showed that lacutamab produced a global objective response rate (ORR) of 28.6% (95% confidence interval [CI], 13.8-50.0) in the KIR3DL2-expressing MF patients (n=21), including 2 complete responses and 4 partial responses.
The Company announced that it will report preliminary data from the Phase 2 TELLOMAK study in Sézary syndrome at the ASH (Free ASH Whitepaper) (American Society of Hematology) 2022 Annual Congress on 10 December. The ASH (Free ASH Whitepaper) abstract states that the preliminary data demonstrate that lacutamab showed clinical activity and a favorable safety profile. In the heavily pre-treated post-mogamulizumab patient population with an average of six prior lines of therapy, in the Intention to treat population (ITT) population, the global confirmed ORR was 21.6% (8/37). Confirmed ORR in the skin was 35.1% (13/37) and confirmed ORR in the blood was 37.8% (14/37). Additional data will be presented at the ASH (Free ASH Whitepaper) 2022 Annual Congress.
On 11 September, at the ESMO (Free ESMO Whitepaper) 2022 conference, the Company presented a poster on the ongoing lacutamab Phase 1b trial design in monotherapy in peripheral T-cell lymphoma (PTCL).
Two clinical trials are underway evaluating lacutamab in patients with KIR3DL2-expressing, relapsed/refractory PTCL:
Phase 1b trial: a Company-sponsored Phase 1b clinical trial to evaluate lacutamab as a monotherapy in patients with KIR3DL2-expressing relapsed PTCL.
Phase 2 KILT (anti-KIR in T Cell Lymphoma) trial: The Lymphoma Study Association (LYSA) investigator-sponsored, randomized trial to evaluate lacutamab in combination with chemotherapy GEMOX (gemcitabine in combination with oxaliplatin) versus GEMOX alone in patients with KIR3DL2-expressing relapsed/refractory PTCL.
ANKET (Antibody-based NK cell Engager Therapeutics):
An 18 October edition of Cell Reports Medicine described the development of Innate’s fit-for-purpose ANKETTM antibody-based tetra-specific molecule to harness the antitumor functions of NK cells, boosting their capacity to proliferate, to accumulate at the tumor site and to kill tumor cells.
Progress continues toward investigational new drug (IND) filing in 2023 for the CD20 targeted tetra-specific ANKETTM, IPH6501.
Sanofi will present two posters on SAR’579/IPH6101 and SAR’514/IPH6401 at the ASH (Free ASH Whitepaper) 2022 Annual Congress on the 11 and 12 December:
An open-label, first-in-human, dose-escalation study of SAR443579 administered as single agent by intravenous infusion in patients with relapsed or refractory acute myeloid leukemia (R/R AML), B-cell acute lymphoblastic leukemia (B-ALL) or high-risk myelodysplasia (HR-MDS)
The Novel Trifunctional Anti-BCMA NK Cell Engager SAR’514 Has Potent in-Vitro and in-Vivo Anti-Myeloma Effect through Dual NK Cell Engagement
The Phase 1/2 clinical trial by Sanofi continues, evaluating IPH6101/SAR’579, the first NKp46/CD16-based CD123-targeted ANKETTM NK cell engager, in patients with relapsed or refractory acute myeloid leukemia (R/R AML), B-cell acute lymphoblastic leukemia (B-ALL) or high-risk myelodysplastic syndrome (HR-MDS).
It was previously announced that Sanofi had made the decision to progress IPH6401/SAR’514 into investigational new drug (IND)-enabling studies. IPH6401/SAR’514 is a BCMA-targeting NK cell engager using Sanofi’s proprietary CROSSODILE multi-functional platform, which comprises the Cross-Over-Dual-Variable-Domain (CODV) format. It induces a dual targeting of the NK activating receptors, NKp46 and CD16, for an optimized NK cell activation, based on Innate’s ANKETTM proprietary platform.
Monalizumab (anti-NKG2A antibody), partnered with AstraZeneca:
Innate continues to see progress for monalizumab in the early non-small cell lung cancer setting, with the ongoing Phase 3 PACIFIC-9 study run by AstraZeneca.
On 12 September at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2022 congress, AstraZeneca presented an oral presentation on the Phase 2 NeoCOAST study assessing the safety and efficacy of neoadjuvant durvalumab in combination with chemotherapy and oleclumab (AstraZeneca’s anti-CD73) or monalizumab and adjuvant treatment in patients with resectable, early-stage NSCLC.
On 1 August, Innate announced that a planned futility interim analysis of the Phase 3 INTERLINK-1 study sponsored by AstraZeneca did not meet a pre-defined threshold for efficacy. The company announced that, based on the result and the recommendation of an Independent Data Monitoring Committee, the study was to be discontinued. There were no new safety findings. AstraZeneca plan to share the data in due course. The INTERLINK-1 study, evaluated monalizumab in combination with cetuximab vs. cetuximab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck who have been previously treated with platinum-based chemotherapy and PD-(L)1 inhibitors.
IPH5201 (anti-CD39), partnered with AstraZeneca:
The previously announced Phase 2 clinical trial conducted by Innate in lung cancer for IPH5201, an anti-CD39 blocking monoclonal antibody developed in collaboration with AstraZeneca, is in planning. The Company will present a poster of preclinical data supporting the rationale for the clinical trial at the 2022 ESMO (Free ESMO Whitepaper) Immuno-Oncology (IO) Annual Congress in December.
AstraZeneca will present a poster entitled "IPH5201 as Monotherapy or in Combination with Durvalumab in Advanced Solid Tumours" at the 2022 ESMO (Free ESMO Whitepaper) IO Annual Congress in December.
IPH5301 (anti-CD73):
The investigator-sponsored Phase 1 trial of IPH5301 (CHANCES), in collaboration with Institut Paoli-Calmettes is ongoing. The trial will be conducted in two parts, Part 1, the dose escalation, followed by a Part 2 safety expansion study cohort. Part 2 will evaluate IPH5301 in combination with chemotherapy and trastuzumab in HER2+ cancer patients. The design of the Phase 1 study will be highlighted at the ESMO (Free ESMO Whitepaper) IO congress in December.
Corporate Update:
On May 03, Innate announced the commencement of an At-The-Market (ATM) program, pursuant to which it may, from time to time, offer and sell to eligible investors a total gross amount of up to $75 million American Depositary Shares ("ADS"). Each ADS representing one ordinary share of Innate. As of September 30, 2022, the balance available under our May 2022 sales agreement remains at $75 million.
Financial Results:
Cash, cash equivalents and financial assets of the Company amounted to €151.4 million as of September 30, 2022. At the same date, financial liabilities amounted to €43.1 million.
Revenues for the first nine months of 2022 amounted to €44.3 million (€10.3 million for the same period in 2021). For the nine-month period, ended September 30, 2022, revenue from collaboration and licensing agreements mainly results from the spreading of the payments received under our agreements with AstraZeneca and Sanofi.