On September 30, 2019 BiomX Ltd., a microbiome company developing both natural and engineered phage therapies, reported that BiomX’s Chief Executive Officer, Jonathan Solomon, will present at the Cantor Fitzgerald Global Healthcare Conference in New York on Wednesday, October 2nd, at 8:55am ET (Press release, BiomX, SEP 30, 2019, View Source [SID1234539963]).

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A webcast of the presentation will be available on the News and Events page of the company’s website at View Source A replay of the webcast will be available approximately two hours after the event and archived on the website for 90 days.

On September 30, 2019 Deciphera Pharmaceuticals, Inc. (Nasdaq:DCPH), a clinical-stage biopharmaceutical company addressing key mechanisms of tumor drug resistance, reported the late-breaking presentation of results from the INVICTUS pivotal Phase 3 clinical study of ripretinib in patients with advanced gastrointestinal stromal tumors (GIST) in an oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress (Press release, Deciphera Pharmaceuticals, SEP 30, 2019, View Source [SID1234539912]).

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"For GIST patients who have failed currently approved agents, there exists an urgent need for effective and well-tolerated treatment options," said Margaret von Mehren, MD, Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. "With a statistically significant improvement observed in progression free survival compared with placebo, and a clinically meaningful increase in overall survival compared with placebo, ripretinib represents a potential standard of care for patients harboring a broad spectrum of mutations known to drive GIST in patients who have no approved treatment options."

"Results from the INVICTUS study support our belief that ripretinib has the potential to transform the current treatment landscape for advanced GIST," said Steve Hoerter, President and Chief Executive Officer of Deciphera. "We are now working with the FDA as we prepare the NDA submission for ripretinib, which we expect in the first quarter of 2020."

Today’s presentation featured new data as well as top-line results previously announced by the Company in August 2019. A copy of the presentation will be available following the session at www.deciphera.com.

INVICTUS Study Results

The INVICTUS Phase 3 clinical study is a randomized (2:1), double-blind, placebo-controlled, international, multicenter study to evaluate the safety, tolerability, and efficacy of ripretinib compared to placebo in 129 patients with advanced GIST whose previous therapies have included at least imatinib, sunitinib, and regorafenib. As previously reported, the study achieved the primary endpoint of improved progression free survival (PFS) compared to placebo in patients with fourth-line and fourth-line plus GIST, as determined by blinded independent central radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Progression Free Survival (PFS)

Ripretinib significantly reduced the risk of disease progression or death by 85% compared to placebo and demonstrated a median PFS of 6.3 months compared to 1.0 month in the placebo arm (HR=0.15, 95% CI (0.09,0.25), p<0.0001). This PFS benefit was consistent across all assessed patient subgroups.

Objective Response Rate (ORR) and Duration of Response

Eight patients (9.4%) had a confirmed objective response with ripretinib (p=0.0504) compared to no confirmed responses in the placebo arm, as measured by blinded independent central review, which was not statistically significant. As of the cutoff date of May 31, 2019, the median duration of response had not been reached with seven of the eight patients still responding to treatment. All responders had partial responses.

Overall Survival (OS)

Ripretinib reduced the risk of death by 64% compared to placebo and demonstrated a median OS of 15.1 months vs. 6.6 months in the placebo arm (HR=0.36, 95% CI (0.20,0.62), nominal p=0.0004). Since statistical significance was not achieved for the secondary endpoint of ORR, the hypothesis testing of OS was not formally performed. According to the pre-specified hierarchical testing procedure of the endpoints, the hypothesis testing of OS cannot be formally conducted unless the test for ORR is statistically significant.

Safety

Ripretinib was generally well tolerated and the adverse events observed in INVICTUS were consistent with data from previously presented Phase 1 study results. Treatment-emergent adverse events (TEAEs) occurred in 99% of patients on the ripretinib arm compared to 98% on the placebo arm. Grade 3 or 4 TEAEs occurred in 49% of patients on the ripretinib arm compared to 44% on the placebo arm. Grade 3 or 4 TEAEs greater than 5% of patients on the ripretinib arm were anemia (9%), abdominal pain (7%) and hypertension (7%). Grade 3 or 4 TEAEs greater than 5% of patients on the placebo arm were anemia (14%). TEAEs leading to dose reduction occurred in 7% of patients on the ripretinib arm compared to 2% on the placebo arm. TEAEs leading to dose interruption occurred in 24% of patients on the ripretinib arm compared to 21% on the placebo arm. TEAEs leading to study treatment discontinuation occurred in 8% of patients on the ripretinib arm compared to 12% of patients on the placebo arm. TEAEs leading to death occurred in 6% of patients on the ripretinib arm compared to 23% on the placebo arm.

New Drug Application (NDA) Submission

Based on the positive INVICTUS data, the Company expects to submit an NDA to the U.S. Food and Drug Administration (FDA) for ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib in the first quarter of 2020.

About the INVICTUS Phase 3 Study

The INVICTUS Phase 3 clinical study is a randomized, double-blind, placebo-controlled, international, multicenter study to evaluate the safety, tolerability, and efficacy of ripretinib compared to placebo in patients with advanced GIST whose previous therapies have included imatinib, sunitinib, and regorafenib. This study was designed to provide evidence of clinical benefit in fourth-line and fourth-line plus patients with GIST that would be required to secure a regulatory approval. Patients were randomized 2:1 to either 150 mg of ripretinib or placebo once daily. The primary efficacy endpoint is progression-free survival (PFS) as determined by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints as determined by independent radiologic review using modified RECIST include Objective Response Rate (ORR), Time to Tumor Progression (TTP) and Overall Survival (OS). See www.clinicaltrials.gov for further information (NCT03353753).

About Ripretinib

Ripretinib is an investigational tyrosine kinase switch control inhibitor that was engineered to broadly inhibit KIT and PDGFRα mutated kinases by using a unique dual mechanism of action that regulates the kinase switch pocket and activation loop. Ripretinib is currently in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, or GIST, systemic mastocytosis, or SM, and other cancers. Ripretinib inhibits initiating and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18, involved in GIST, as well as the primary D816V exon 17 mutation involved in SM. Ripretinib also inhibits primary PDGFRα mutations in exons 12, 14 and 18, including the exon 18 D842V mutation, involved in a subset of GIST. In June 2019, the U.S. FDA granted Fast Track Designation to ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib.

Deciphera Pharmaceuticals has an exclusive license agreement with Zai Lab (Shanghai) Co., Ltd. for the development and commercialization of ripretinib in Greater China (Mainland China, Hong Kong, Macau and Taiwan). Deciphera Pharmaceuticals retains development and commercial rights for ripretinib in the rest of the world.

On September 30, 2019 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical stage immuno-oncology company, reported preliminary results from its ongoing Phase 2 basket trial, evaluating DPX-Survivac in combination with Merck’s Keytruda (pembrolizumab) and intermittent low dose cyclophosphamide (CPA) in patients with advanced and metastatic solid tumors (Press release, IMV, SEP 30, 2019, View Source [SID1234539946]). The data were presented during the Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) poster session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress, being held September 27 – October 1, 2019, in Barcelona, Spain.

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"We are encouraged by the initial response observed from these preliminary data, which feature a safety profile consistent with observations across other studies of DPX-Survivac as well as promising signs of clinical activity. Importantly, these results expand our clinical dataset into four additional hard-to-treat solid tumor indications, as we continue to explore the broad potential of our targeted T cell therapy in more than 20 solid and hematological tumor types that express survivin," said Frederic Ors, IMV’s Chief Executive Officer. "Later this year, we anticipate additional data from ongoing studies of DPX-Survivac in our lead indications – including topline results from DeCidE1, a Phase 2 study evaluating DPX-Survivac in ovarian cancer, and updated results from SPiRel, a Phase 2 study evaluating DPX-Survivac in combination with Keytruda in r/r DLBCL – both of which have demonstrated this program’s potential to safely generate a durable clinical response."

Preliminary Results from the Phase 2 Basket Trial

At the time of cut-off, 23 patients were enrolled across all five patient cohorts. This includes 19 patients across all cohorts who received DPX-Survivac in combination with pembrolizumab with CPA, and four patients from the ovarian cancer cohort receiving DPX-Survivac with only pembrolizumab:

Preliminary results from the first on-study scan showed tumor reduction in patients with ovarian cancer (with and without CPA), non-small cell lung cancer (NSCLC) and bladder cancer;
Partial responses observed at first scan in two subjects (bladder cancer, ovarian cancer); 19/23 subjects are still active on study treatment.
T cell infiltration observed in biopsy samples from subjects who achieved tumor reduction on treatment;
Eight ovarian cancer patients were enrolled in the study, randomized 1:1 to treatment with and without CPA. Tumor control and tumor reductions were observed in both groups; and
Safety evaluation on all evaluable patients demonstrated that treatment was well-tolerated, with no related Grade 3-4 or immune-related adverse events (AEs) reported.
The poster is available on the Investors section of the company’s website, under "Events, Webcasts & Presentations" at www.imv-inc.com.

About the Phase 2 Basket Trial

IMV’s Phase 2 basket trial is an open label, multi-center study, evaluating DPX-Survivac across five cohorts of patients with bladder cancer, liver cancer (hepatocellular carcinoma), ovarian cancer (with and without CPA), NSCLC and tumors shown to be positive for the microsatellite instability high (MSI-H) biomarker.

Subjects will receive DPX-Survivac (SC: 2 x 0.25 mL every three weeks, followed by up to 11 x 0.1 mL every nine weeks), in combination with pembrolizumab (IV: 200 mg every 3 weeks cycle) and CPA (oral: 50 mg BID on alternating weeks) across five cohorts of patients with bladder cancer, liver cancer (hepatocellular carcinoma), ovarian cancer, NSCLC and tumors shown to be positive for the microsatellite instability high (MSI-H) biomarker. The study is designed to assess primary endpoints of safety and objective response rate (ORR), with multiple secondary and exploratory measures.

The study included a safety lead-in, which included 20 patients from all five cohorts. The five cohorts are now expanded to recruit additional subjects following a Simon two stage design. Enrollment in the ovarian cancer cohort will be randomized 1:1 into two arms with and without CPA. All other cohorts will utilize a single-arm design and administer treatment with the triple combination. As of Sept. 27th, 2019, 28 patients are enrolled (50 were screened). IMV expects to enroll 184 patients across clinical sites in the U.S. and Canada.

About DPX-Survivac

DPX-Survivac is the lead candidate in IMV’s new class of immunotherapies that programs targeted T cells in vivo. It has demonstrated the potential for industry-leading targeted, persistent, and durable T cell activation. IMV believes this mechanism of action (MOA) is key to generating durable solid tumor regressions. DPX-Survivac consists of survivin-based peptides formulated in IMV’s proprietary DPX drug delivery platform. DPX-Survivac is designed to work by eliciting a cytotoxic T cell immune response against cancer cells presenting survivin peptides on their surface.

Survivin, recognized by the National Cancer Institute (NCI) as a promising tumor-associated antigen, is broadly over-expressed in most cancer types, and plays an essential role in antagonizing cell death, supporting tumor-associated angiogenesis, and promoting resistance to chemotheratherapies. IMV has identified over 20 cancer indications in which survivin can be targeted by DPX-Survivac.

DPX-Survivac has received Fast Track designation from the U.S. Food and Drug Administration (FDA) as maintenance therapy in advanced ovarian cancer, as well as orphan drug designation status from the U.S. FDA and the European Medicines Agency (EMA) in the ovarian cancer indication.

On September 30, 2019 Rakuten Medical, a clinical-stage, global biotechnology company developing precision-targeted cancer therapies based on its proprietary, anti-cancer treatment platform, Illuminox, reported post-hoc analysis of safety, pharmacokinetic (PK), immunogenicity and exploratory biomarker data from its RM-1929 photoimmunotherapy (PIT) Phase 1 & 1/2a studies (Press release, Rakuten Medical, SEP 30, 2019, View Source [SID1234539930]). These early clinical trials evaluated the safety and anti-tumor activity of RM-1929 PIT in patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC).

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The key findings were presented during two poster presentations at the 2019 ESMO (Free ESMO Whitepaper) Congress held this week in Barcelona:

"Integrated safety, pharmacokinetics (PK) and immunogenicity data of RM-1929 photoimmunotherapy (PIT) in subjects with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC)" (Abstract 2954), presented by Jennifer M. Johnson, MD, PhD, FACP; Assistant Professor, Department of Medical Oncology and Associate Program Director, Hematology and Medical Oncology Fellowship, Thomas Jefferson University.

The assessment of safety and PK across the Phase 1 & 1/2a studies, when considered in connection with preliminary Phase 2a clinically meaningful anti-tumor activity reported at ASCO (Free ASCO Whitepaper) 2019, support the current global Phase 3 study of ASP-1929 Illuminox treatment in locoregional rHNSCC patients. Specifically:

Out of the 41 patients in the trial, 17 experienced at least one serious adverse event (SAE), and five experienced SAE considered related to study treatment; the majority being local to the treatment site.
RM-1929 PIT 640 mg/m2 dose achieved an AUC and T1/2, which is expected to achieve saturation of the epidermal growth factor receptors (EGFR). Repeated administration of RM-1929 PIT (cycle 2-4) given approximately four weeks apart, were comparable to those in cycle one, with a low presence of anti-drug antibodies (ADA).
"Intratumoral and peripheral exploratory biomarker analysis in patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC) treated with RM-1929 photoimmunotherapy" (Abstract 3725), presented by Jack Bui, MD, PhD, Pathology; University of California San Diego Health.

Immune-activation biomarkers following RM-1929 PIT treatment were evaluated in the Phase 1/2a study in patients with rHNSCC; conclusions indicated that certain subsets of patients displayed potential signs of immune activation following treatment, regardless of best target tumor response. More specifically:

RM-1929 PIT was associated with induction of PD-L1 expression in tumor and immune cells in eight out of 12 patients.
EGFR expression was maintained in residual tumors in 12 patients with pre- and post-treatment biopsies, indicating that target lesions may be candidates for additional PIT treatment cycles.
Peripheral blood immunophenotyping suggests possible activation of innate and adaptive immunity following treatment in 15 of 18 patients.
"Rakuten Medical is encouraged by these post-hoc analyses across our available early studies, as they further characterize the safety and PK, and provide insights into potential immune activation by RM-1929 PIT that could potentially enable further development in combination with other anti-cancer, immunotherapy treatment options," said Jeannie Hou, VP of Clinical Development at Rakuten Medical. "Our ASP-1929 Illuminox Phase 3 clinical trial is currently underway, which is another important step in the development of a possible new therapeutic option for head and neck cancer patients; and may provide those suffering from this devastating disease with an additional therapeutic choice."

On September 30, 2019 Iksuda Therapeutics (Iksuda), a developer of next generation Antibody Drug Conjugates (ADCs), reported the first data on its lead ADC, IKS01. IKS01, an ADC targeting the folate receptor, has shown significant anti-tumour efficacy in pre-clinical models of ovarian and lung tumours, each of which included a broad range of folate-receptor alpha (FRA) expression (Press release, Iksuda Therapeutics, SEP 30, 2019, View Source [SID1234539947]). The data is currently being presented at ESMO (Free ESMO Whitepaper) Congress 2019 in Barcelona, Spain.

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ADCs allow for the targeted delivery of a potent cytotoxic payload to tumours, resulting in selective killing with increased efficacy and less off-target toxicity than standard-of-care chemotherapies. Frequent over-expression of FRA in ovarian and non-small-cell lung cancer (accounting for 80% of lung cancer cases) and relative lack of expression in normal tissue, make it an attractive therapeutic target. However, anti-tumour activity is generally limited to patients whose tumours express high levels of FRA.

IKS01 is an ADC comprised of an FRA-targeting antibody conjugated via Iksuda’s PermaLink technology to Femtogenix’s highly potent FGX2-62 payload. IKS01 is target specific and these new data confirm that it is highly effective in causing tumour regression in FRA-expressing models at doses that are well-tolerated, significantly more active than a benchmark ADC and caused complete regressions in low/moderate FRA-expressing models.

The IKS01 data is a major advancement of Iksuda’s ADC drug pipeline, from which it aims to progress multiple candidates towards first clinical studies in 2020.

Dave Simpson PhD, Chief Executive Officer, Iksuda Therapeutics, said: "Ovarian cancer is one of the most deadly gynaecological cancers and lung cancer remains a leading cause of cancer-related death. The IKS01 data highlight the potential impact of our ADC pipeline by targeting difficult-to-treat tumours and advancing current standard of care."

Iksuda Therapeutics’ will be exhibiting its poster: ‘IKS01, a next generation antibody drug conjugate (ADC) designed to be efficacious in tumors with low and moderate levels of folate receptor alpha (FRA) expression’ until 1st October at ESMO (Free ESMO Whitepaper) Congress 2019, presentation number 58P.