On April 28, 2023 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the U.S. Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC), by a vote of 11 to 1 with one abstention, supported FDA approval of LYNPARZA plus abiraterone and prednisone or prednisolone (abi/pred) for the first-line treatment of adult patients with BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC) (Press release, Merck & Co, APR 28, 2023, View Source [SID1234630673]). The committee voted that FDA should restrict use of LYNPARZA plus abi/pred to these BRCAm mCRPC patients, recommending against approval beyond this patient population.

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In August 2022, the FDA accepted the supplemental New Drug Application for LYNPARZA plus abi/pred for priority review based on positive results from the pivotal Phase 3 PROpel trial, which were also published in NEJM Evidence. The ODAC provides the FDA with independent, expert advice and recommendations on marketed and investigational medicines for use in the treatment of cancer. The FDA is not bound by the committee’s guidance but takes its advice into consideration. AstraZeneca and Merck will continue to work with the FDA as the agency completes its review of the application.

Neal Shore, chief medical officer of urology and surgical oncology for GenesisCare, US and PROpel trial investigator, said, "Today’s recommendation by the ODAC is disappointing news for clinicians and prostate cancer patients alike. Preventing or delaying radiographic progression is an important clinical endpoint in assessing oncologic treatment and is very relevant to patients, their caregivers and their families. It is essential that physicians and their patients have an opportunity to choose treatment with the goal of optimizing cancer care outcomes."

Susan Galbraith, executive vice president, oncology R&D, AstraZeneca, said, "Novel treatments are urgently needed for patients with metastatic castration-resistant prostate cancer. While we are pleased with the recognition of the benefit of LYNPARZA plus abiraterone for patients with BRCA-mutated metastatic castration-resistant prostate cancer, we are disappointed with the outcome of today’s ODAC meeting. We strongly believe in the results of the PROpel trial, which demonstrated a clinically meaningful benefit for this combination in a broad population of patients regardless of biomarker status."

Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, said, "With the incidence and mortality of prostate cancer set to double in the coming decades, it is critical that we bring new treatment options with the potential to reduce the risk of disease progression or death to patients at the earliest possible moment in their care. Though we are pleased that the ODAC recommended LYNPARZA for patients with mCRPC who have BRCA mutations, we believe in the potential of LYNPARZA plus abi/pred for a broad range of patients with mCRPC, based on the results of PROpel. We look forward to the outcome of the FDA’s review of the application."

Results from the PROpel trial showed a statistically significant and clinically meaningful 34% reduction in the risk of radiographic disease progression or death with LYNPARZA plus abi/pred (HR=0.66 [95% CI, 0.54-0.81]; p<0.001) versus placebo plus abi/pred in patients with mCRPC. Median radiographic progression-free survival (rPFS) was 24.8 months versus 16.6 months, respectively.

Further results from the final pre-specified overall survival (OS) analysis were presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (maturity 47.9%, HR=0.81 [95% CI, 0.67-1.00]; p=0.0544). While the observed 7.4-month numerical increase in median OS did not achieve statistical significance, the totality of the efficacy results from PROpel build on the meaningful gains achieved for patients in this setting versus patients treated with abi/pred alone, a current standard of care.

In exploratory analyses of the BRCAm subgroup, patients in the LYNPARZA plus abi/pred arm had fewer rPFS (HR=0.23 [95% CI, 0.12-0.43]) and OS (HR=0.29 [95% CI, 0.14-0.56]) events versus those receiving placebo plus abi/pred. In the subgroup of patients who tested negative for BRCAm by either a tumor tissue-based test or a circulating tumor DNA test, patients in the LYNPARZA plus abi/pred arm also had fewer rPFS events (HR=0.76 [95% CI, 0.61-0.94] versus those receiving placebo plus abi/pred, as well as modestly fewer OS events (HR=0.91 [95% CI, 0.73-1.13]).

The safety and tolerability of LYNPARZA plus abi/pred in PROpel 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 (49.7%), fatigue (38.7%), nausea (30.7%), back pain (21.6%) and diarrhea (20.6%). Grade ≥3 AEs were anemia (16.1%), hypertension (3.8%), urinary tract infection (2.5%), fatigue (2.5%), vomiting (1.5%), diarrhea (1.3%), decreased appetite (1%), back pain (1%) and nausea (0.3%). Approximately 17% of patients who received LYNPARZA in combination with abi/pred discontinued treatment due to an AE.

LYNPARZA in combination with abi/pred is approved in the European Union and several other countries for the treatment of adult patients with mCRPC based on the PROpel trial. In the U.S., LYNPARZA is currently approved for patients with homologous recombination repair gene-mutated mCRPC who have progressed following prior treatment with enzalutamide or abiraterone based on the Phase 3 PROfound trial. For that U.S. indication, patients are selected for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

About PROpel

PROpel is a randomized, double-blind Phase 3 trial testing the efficacy, safety and tolerability of LYNPARZA versus placebo when given in addition to abi/pred in patients with mCRPC who had not received prior chemotherapy or new hormonal agents in the mCRPC setting. The major efficacy outcome was rPFS as assessed by investigator per RECIST v1.1 and Prostate Cancer Working Group (bone) criteria. OS was an additional efficacy outcome measure.

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.

Venous Thromboembolic Events (VTE): Including severe or fatal pulmonary embolism (PE) occurred in patients treated with LYNPARZA. VTE 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.

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.

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 and at a ≥5% frequency compared to 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

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

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 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 prostate cancer are estimated to develop castration-resistant prostate cancer (CRPC) within five years, with at least 84% of these patients presenting with metastases at the time of CRPC diagnosis. Of patients with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.

On April 28, 2023 Isofol Medical AB (publ), (Nasdaq Stockholm: ISOFOL), reported that the company has initiated a preclinical research collaboration with the Norwegian biotech company Oncosyne AS, to evaluate the effect of the drug candidate arfolitixorin in different doses combined with the cancer drug 5-FU, among others (Press release, Isofol Medical, APR 28, 2023, View Source [SID1234630672]). This is an important step in the company´s previously communicated strategy to re-evaluate possible future tracks for arfolitixorin and to maximize the opportunities to take the drug candidate further toward potential market approval.

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Isofol, together with external experts, is conducting an extensive analysis of the data from the clinical phase III study, AGENT. In the study, arfolitixorin did not meet its goals and the study was terminated in 2022. The initial conclusions from the analysis indicate that the dose of arfolitixorin may have been too low to allow a fair comparison with the control group and that the substance may not have been administrated optimally. Arfolitixorin’s safety profile was a prioritized part of the analysis, and the company has not found any obstacles to proceed with the development of the drug candidate.

Based on the initial analysis of data from the AGENT study, Isofol intends to evaluate several doses of arfolitixorin in combination with 5-FU as well as other possible treatments, within a research collaboration with the Norwegian biotech company Oncosyne.

Oncosyne AS has developed a technology platform for preclinical testing in functional precision oncology, based on drug screening of the patient’s own cancer cells. The technology can be used in several stages of drug development from functional evaluation of drug activity to selection of patients for clinical trials.

" Initial outcomes from the comprehensive analysis of phase III data conducted in collaboration with leading external experts provide support for initiating a preclinical evaluation of the drug candidate. Oncosyne has developed a technology platform that quickly and cost-effectively can provide an answer to whether a different dosage regiment could strengthen the future potential of arfolitixorin," says Thomas Andersson, CEO of Isofol.

On April 28, 2023 INOVIO (NASDAQ: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-associated diseases, cancer, and infectious diseases, reported that first quarter 2023 financial results will be released after the market close on May 10, 2023 (Press release, Inovio, APR 28, 2023, View Source [SID1234630671]). Following the release, INOVIO will host a live conference call and webcast at 4:30 p.m. ET to discuss financial results and provide a general business update.

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A live and archived version of the audio presentation will be available online at View Source This is a listen-only event but will include a live Q&A with analysts.

On April 28, 2023 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel LAG-3 related immunotherapy treatments for cancer and autoimmune diseases, reported an update on the ongoing development of its product candidates, eftilagimod alpha (efti) and IMP761 for the quarter ended 31 March 2023 (Q3 FY23) (Press release, Immutep, APR 28, 2023, View Source [SID1234630668]).

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EFTI DEVELOPMENT PROGRAM FOR CANCER

Immutep made strong progress during the quarter to advance its clinical development strategy to position the company, or a potential partner, to fully exploit efti’s broad potential.

AIPAC-003 — Phase II/III trial in Metastatic Breast Cancer (MBC)

In March, Immutep initiated AIPAC-003 (Active Immunotherapy PAClitaxel), its integrated Phase II/III trial evaluating efti in combination with paclitaxel for the treatment of HER2-neg/low metastatic breast cancer and triple-negative breast cancer. These two indications account for ~78% of breast cancer cases. The trial commenced following the regulatory approval in the United States and Institutional Review Board (IRB) approval in Spain. Immutep anticipates enrolling the first patient in Q2 CY2023.

As a first-in-class soluble LAG-3 protein targeting MHC Class II ligands on antigen-presenting cells (APC), efti is well positioned to improve clinical outcomes from standard-of-care chemotherapy due to its unique mechanism of action. Its activation of APC triggers a broad immune response that includes significant increases in cytotoxic CD8+ T cells armed with chemo-induced tumour antigens to target cancer.

The AIPAC-003 trial employs an integrated clinical design agreed to with the FDA to help inform a potential Biologics License Application (a request for permission to sell a biologic product) and a potential Marketing Authorisation Application with the European Medicines Agency (EMA). This trial design also allows for a risk-balanced approach with the Phase III portion dependent on the Phase II results, among other items.

TACTI-002 (also designated KEYNOTE-PN798) Phase II clinical trial

Positive final data on safety and efficacy was reported from Part B of the TACTI-002 trial in patients with 2nd line non-small cell lung cancer (NSCLC) refractory to anti-PD-(L)1 therapies in a Mini Oral presentation at ESMO (Free ESMO Whitepaper)’s European Lung Cancer Congress (ELCC) 2023. These patients have few therapeutic options, and the addition of efti to pembrolizumab may help these patients by reverting the confirmed anti-PD-(L)1 therapy resistance.

The Company reported encouraging clinical results, including an Overall Survival (OS) rate of 39% at 21 months. In addition, 83% of patients studied for Tumour Growth Kinetics showed deceleration (50%) in tumour growth or shrinkage (33%) of target lesions. Responses were confirmed and durable with responders participating in the study for more than 19 months.

The ORR, PFS, and OS were more pronounced in patients with high PD-L1 expression (N=6) or who were secondary resistant (N=25). For patients with ≥50% PD-L1 TPS expression, median OS was not yet reached, overall response rate (ORR) was 33.3%, and 6-month progression-free survival (PFS) was 50%. Efti plus pembrolizumab was well tolerated without any new safety signals, and there was no treatment discontinuation due to adverse reactions.

TACTI-003 – Phase IIb clinical trial in 1st line HNSCC

In early 2023 Immutep announced it has successfully enrolled over 50% of the planned 154 patients into the randomised Phase IIb TACTI-003 trial. Subsequent to quarter end TACTI-003 has reached 75% enrolment, and Immutep expects to complete enrolment by mid-year positioning the Company to report top-line results in H2 of CY2023.

Planned late-stage trial in 1st line NSCLC

Immutep is continuing its preparations for a late-stage trial evaluating efti in 1st line NSCLC in combination with anti-PD-1 therapy. The NSCLC program will be shaped by the maturing data from the Company’s ongoing TACTI-002 and INSIGHT-003 trials. Current activity is focused on trial design and engagement with regulatory authorities and other stakeholders. The Company obtained US FDA Fast Track designation late last year for this indication.

INSIGHT-003 – Phase I in 1st line NSCLC

In February, the investigator-initiated INSIGHT-003 trial reached its enrolment target of 20 patients with 1st line NSCLC for this first triple combination therapy study of efti with standard-of-care combination of anti-PD-1 therapy and chemotherapy. INSIGHT-003 has been now extended to include a total of 50 patients. The expansion of INSIGHT-003 will further inform planning for registrational studies.

IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASES

During the first quarter, our preclinical development continued for IMP761, including preparations to begin the toxicology study. As the first immunosuppressive agonist antibody to LAG-3 acting upstream on activated T cells to target the root cause of self-antigen-specific T cell induced disease, IMP761 is a potential game-changer in how autoimmune diseases are treated. The Company currently anticipates that clinical development will begin in the first half of CY2024.

INTELLECTUAL PROPERTY

During the quarter, Immutep was granted three new patents directed to efti. The first is a United States patent drawn to methods of treating cancer with a combination of efti and chemotherapy, where the efti is administered in a dose of more than 6 mg. This is the third United States patent granted from this family.

The second patent is an Indian patent that protects Immutep’s intellectual property relating to combined preparations of efti with a PD-1/PD-L1 therapy for the treatment of cancer or infection. The third patent is an Australian patent which relates to a potency assay for release testing of efti. The assay is used in Immutep’s commercial-scale (2,000L) manufacturing process. This new Australian patent follows the grant of a similar patent in South Korea in 2022.

BOARD AND MANAGEMENT CHANGES

On 11 April, Lis Boyce was appointed as Non-Executive Director replacing Lucy Turnbull, who re-joined the board after the sudden and untimely death of Grant Chamberlain in January 2022. The Board is grateful to Lucy for stepping in under such tragic circumstances and for her boundless energy and valued insights.

Ms Boyce is a highly experienced corporate lawyer and currently a partner at Piper Alderman. She has extensive experience in the Life Sciences and Healthcare sectors as well as in capital raisings, strategic collaborations, commercial contracts and mergers and acquisitions. Lis is currently deputy chair of AusBiotech’s AusMedtech Advisory Group and a member of AusBiotech’s State Committee for NSW.

On 26 April, Immutep announced that it expanded its leadership team with the appointment of Florian D. Vogl, M.D., Ph.D., MSc., as Chief Medical Officer (CMO) with effect from 1 May 2023. Dr. Vogl has over a decade of experience in the biopharmaceutical industry with extensive clinical development expertise in the field of oncology. Most recently, he was CMO of Cellestia Biotech where he focused on delivering new treatments to patients with cancer and autoimmune disorders that had limited therapeutic options. Prior to Cellestia, Dr. Vogl held senior management roles in Europe and the United States, including Head of Clinical Development Europe at Rainier Therapeutics, Senior Global Medical Leader, Oncology Development at Novartis, and as Early Development Leader, Oncology Pipeline at Amgen.

Dr. Vogl assumes the CMO role from Frédéric Triebel, M.D., Ph.D., who previously acted as both Chief Scientific Officer (CSO) and CMO of Immutep. Dr. Triebel’s foremost focus will be on his responsibilities as CSO and as a member of Immutep’s Board.

FINANCIAL SUMMARY

Immutep continued to focus on prudent cash management during the past quarter (Q3 FY23). The Company remains well funded with a cash runway extending to the end of FY24.

Cash receipts from customers in the quarter increased to $30k, compared to $8k in Q2 FY23. The net cash used in G&A activities in the quarter was $1.12million compared to $734k in Q2 FY23. Payments to Related Parties, detailed in Item 6 of the Appendix 4C cash flow report for the quarter, includes $257k in payments for Non-Executive Director’s fees and Executive Director’s remuneration.

The net cash used in R&D activities in the quarter was $11.52 million, compared to $5.87 million in Q2 FY23. The increase was mainly due to the increased clinical trial and manufacturing activities.

Total net cash outflows used in operating activities in the quarter were $14.17 million compared to $7.02 million in Q2 FY23.

Immutep’s cash and cash equivalent balance at 31 March 2023 was approximately $55.2 million, giving the Company an expected cash reach based on current estimates to June 2024. Immutep will continue to manage its solid cash balance carefully as it pursues its overall clinical development strategy.

A copy of the Appendix 4C — Quarterly Cash Flow Report for the quarter is attached.

On April 28, 2023 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported recent progress in the business and announced financial results for the quarter ended March 31, 2023 (Press release, ImmunoGen, APR 28, 2023, View Source [SID1234630667]).

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"With a strong first full quarter of sales and continued momentum in FRα testing and market access, we have started the year making great strides towards establishing ELAHERE as the standard of care for FRα-positive ovarian cancer," said Mark Enyedy, ImmunoGen’s President and Chief Executive Officer. "Our commercial and medical teams have delivered exemplary performances in the first stages of the ELAHERE launch and we look forward to continued success with the appointment of Isabel Kalofonos as our new Chief Commercial Officer."

Enyedy continued, "With our goal of obtaining full approval for ELAHERE in the US and expanding into Europe, we expect to announce top-line data from our confirmatory MIRASOL trial in early May. In parallel, we advanced our broader development program to move into platinum-sensitive disease and position ELAHERE as the combination agent of choice in ovarian cancer. Turning to our second pivotal program, PVEK, we expect to complete enrollment in our pivotal CADENZA trial in frontline BPDCN by the end of the year. In addition, we anticipate reporting data from our expansion cohorts with the PVEK/VEN/AZA triplet in frontline AML at ASH (Free ASH Whitepaper) in December. We also advanced dose escalation with IMGN151, our second-generation ADC targeting FRα, and expect to report data for IMGC936 following an interim analysis. With meaningful clinical milestones coming, strong commercial uptake of ELAHERE, and a strengthened balance sheet following our recent non-dilutive term loan financing with Pharmakon, we are well positioned to create significant value for both patients and shareholders throughout the year."

RECENT PROGRESS

Generated $29.5 million in ELAHERE (mirvetuximab soravtansine-gynx) net sales for the quarter ended March 31, 2023, the first full quarter of launch following approval in November of 2022.
Reached requisite number of progression-free survival (PFS) events in the confirmatory MIRASOL trial.
Presented final overall survival and additional efficacy data from the SORAYA trial at the Society of Gynecologic Oncology (SGO) 2023 Annual Meeting.
Advanced dose escalation with IMGN151 and enrollment in the non-small cell lung cancer (NSCLC) expansion cohort for IMGC936.
Announced non-dilutive credit facility with Pharmakon Advisors, LP for up to $175 million; $75 million received upon execution.
Appointed Isabel Kalofonos as Senior Vice President and Chief Commercial Officer.
ANTICIPATED UPCOMING EVENTS

Report top-line data for MIRASOL trial in early May 2023.
Submit Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for ELAHERE in FRα-high platinum-resistant ovarian cancer (PROC) in the second half of 2023 to support approval and launch in Europe.
Submit supplemental Biologics License Application (sBLA) to the FDA in the second half of 2023 to support the conversion of the accelerated approval of ELAHERE to full approval.
Our partner, Huadong Medicine, to submit Biologics License Application (BLA) to the National Medical Products Administration (NMPA) of China for ELAHERE in FRα-high PROC in the second half of 2023 to support potential approval and launch.
Report on primary endpoint for PICCOLO, a single-arm Phase 2 trial of mirvetuximab in FRα-high platinum-sensitive ovarian cancer (PSOC), before the end of 2023.
Complete enrollment in the pivotal Phase 2 CADENZA trial this year.
Initiate combination cohort of pivekimab with magrolimab in relapsed/refractory (R/R) acute myeloid leukemia (AML) in collaboration with Gilead in the second half of 2023.
Report data from two cohorts evaluating the pivekimab triplet with Venclexta (venetoclax) and Vidaza (azacitidine) in frontline AML at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December.
Report data from the IMGC936 NSCLC cohort following an interim analysis.
FINANCIAL RESULTS

Total revenues were $49.9 million for the quarter ended March 31, 2023, including $29.5 million of net product revenues from sales of ELAHERE for the first full quarter of launch following approval in November 2022, compared to $38.1 million in total revenue for the quarter ended March 31, 2022. The increase was primarily driven by ELAHERE net sales and recognition of a $15 million upfront fee received pursuant to a multi-target license and option agreement executed in the first quarter with Vertex Pharmaceuticals, partially offset by $30.8 million of license fees recorded as revenue in the prior year period pursuant to the Company’s collaboration and license agreements with Huadong Medicine and Eli Lilly.

Research and development expenses rose to $51.6 million for the quarter ended March 31, 2023 compared to $44.3 million for the quarter ended March 31, 2022. The increase was primarily driven by costs related to the addition of our medical affairs organization and clinical trial expenses.

Selling, general and administrative expenses were $40.0 million for the quarter ended March 31, 2023 compared to $16.6 million for the quarter ended March 31, 2022. The increase was due primarily to greater expenses in support of the US launch of ELAHERE, including costs related to the addition of our commercial organization and sales and marketing activities.

Net loss for the first quarter of 2023 was $41.0 million, or $0.16 per diluted share, compared to net loss of $24.1 million, or $0.10 per diluted share, for the first quarter of 2022.

ImmunoGen had $201.2 million in cash and cash equivalents as of March 31, 2023, compared with $275.1 million as of December 31, 2022. Cash used in operations was $73.7 million for the first three months of 2023 compared with cash used in operations of $41.4 million for the same period in 2022. Capital expenditures were $0.2 million and $0.3 for the first three months of 2023 and 2022, respectively. Earlier this month, the Company entered into a term loan credit facility for up to $175 million with entities managed by Pharmakon and drew the initial tranche of $75 million upon execution of the facility.

FINANCIAL GUIDANCE

ImmunoGen has updated its financial guidance for 2023 and now expects:

revenues, excluding product revenue from ELAHERE, between $45 million and $50 million; and
operating expenses between $320 million and $335 million.
ImmunoGen expects to provide ELAHERE product revenue guidance later this year. The increase in revenue guidance is a result of recognizing a $15 million upfront fee from Vertex in the first quarter as no deferral was required. Additionally, the Company increased its operating expense guidance to reflect greater spend in support of ELAHERE’s launch and expected growth trajectory.

ImmunoGen expects that its current cash, inclusive of the $75 million received pursuant to the term loan facility with Pharmakon, and combined with anticipated product and collaboration revenues, will fund operations into 2025.

CONFERENCE CALL INFORMATION

ImmunoGen will hold a conference call today at 8:00 a.m. ET to discuss these results. To access the live call by phone, please register here. A dial-in and unique PIN will be provided to join the call. The call may also be accessed through the Investors and Media section of the Company’s website, www.immunogen.com. Following the call, a replay will be available at the same location.

ABOUT ELAHERE

ELAHERE (mirvetuximab soravtansine-gynx) is a first-in-class ADC comprising a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells.

ELAHERE is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Eye problems are common with ELAHERE and can be severe. ELAHERE also can cause severe or life-threatening inflammation of the lungs that may lead to death and patients may develop nerve problems called peripheral neuropathy during treatment. Please see full Prescribing Information, including Boxed Warning, and Medication Guide for ELAHERE.