On August 5, 2019 MOLOGEN AG (ISIN DE000A2LQ900, SIN A2L Q90) reported the top line data of its pivotal phase III IMPALA study (Press release, Mologen, AUG 5, 2019, View Source [SID1234538145]). The study compares the TLR9 agonist lefitolimod (MGN1703) with local standard of care as a maintenance therapy in patients with metastatic colorectal cancer presenting with an objective tumor response following first-line induction therapy. The primary endpoint – overall survival (OS) – was not met showing a median OS of 22.0 and 21.9 months in the lefitolimod and control group respectively (p=0.2765; HR=1.12; 95% CI 0.91 – 1.38). Timepoint related OS and predefined sub-group analyses did also not indicate a benefit, while regarding Progression Free Survival (PFS) standard of care was superior to lefitolimod treatment. No new safety signals were detected; hence the favorable safety and tolerability profile was confirmed.

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MOLOGEN is a pioneer in the field of immunotherapy, especially in the TLR9 field with the product family of DNA-based TLR9 agonists including its lead compound lefitolimod, as well as its follow-up molecules EnanDIM. Given its mode of action and confirmed favorable safety profile, lefitolimod is being used as combination partner in anti-cancer and anti-HIV immunotherapies.

Dr med Stefan M. Manth, CEO of MOLOGEN, noted: "We are disappointed with these top-line results and will now analyze the bountiful data coming out of IMPALA in depth. We will then build on these analyses from IMPALA to further inform the development of lefitolimod and its successor molecules from the EnanDIM platform for cancer and HIV patients. We are grateful to the patients and investigators for their participation in this important study."

Dr med Matthias Baumann, CMO of MOLOGEN, stated: "Unfortunately the positive results in our single agent lefitolimod phase II IMPACT study did not translate into a successful outcome of our phase III IMPALA trial despite the fact that all learnings have been incorporated into the trial design. In contrast to the time when the IMPALA design was conceived, it now appears that for successful anti-cancer immunotherapies a combination approach is of paramount importance. Due to the large body of evidence indicating the potential of TLR9 agonism in this context we remain committed to the further development of our candidates."

The detailed data from this first top line analysis of the IMPALA trial will be submitted for presentation at an upcoming international scientific congress.

Strategic focus on combination therapies in indications with high medical need and significant market potential

In light of these results the strategy of MOLOGEN going forward will focus on combination approaches for both lefitolimod and the first clinical candidate from the EnanDIM family in ongoing and planned clinical trials. This strategy serves as cornerstone for ongoing licensing and funding efforts.

Further to the IMPALA single-agent approach, lefitolimod is currently being evaluated in a phase I/II clinical study in combination with the checkpoint inhibitor Yervoy (ipilimumab) in a broader variety of solid tumors. The study is being conducted at the renowned MD Anderson Cancer Center, Texas, USA. In addition to studies in the field of oncology, lefitolimod has also been tested in HIV patients in a phase Ib/IIa study, the TEACH trial. Based on the encouraging study results, lefitolimod will be investigated in a phase IIa combination study, the TITAN trial, in HIV-infected patients in combination with innovative virus-neutralizing antibodies developed by the Rockefeller University in New York, USA. The trial will be conducted in cooperation with the Aarhus University Hospital in Denmark, which was also the academic partner of MOLOGEN in the TEACH trial. TITAN is funded by the US biotech company Gilead Inc. Furthermore, plans for another clinical combination study in HIV with a prominent US center are at an advanced stage.

The next generation TLR9 agonistic molecules of the EnanDIM-family coming out of the research labs of MOLOGEN offer additional potential for development in various cancer indications and HIV. A first clinical candidate from the EnanDIM platform is presently in late pre-clinical testing and expected to launch into clinical development in oncology at the end of 2019.

Checkpoint inhibitors alone are expected to generate sales of approximately US$ 25 billion by 2022 (acc. to Research and Markets) in a growing variety of indications. However, the greatest potential of checkpoint inhibitors is still to be realized, i.e. with adequate combination partners to target indications non-amenable to checkpoint inhibitor monotherapy. Estimates from the market research organization Research and Markets project that the market for cancer immunotherapies could rise to more than US$100 billion by 2024.

Background to the IMPALA study

IMPALA (Immunomodulatory MGN1703 in Patients with Advanced Colorectal Carcinoma with tumor reduction during induction treatment) is a pivotal, randomized, international, multicenter, open-label phase III trial. The study involves more than 540 patients from eight European countries, including the five major European pharmaceutical markets. Recruitment was completed in May 2017. The study includes patients with metastatic colorectal cancer who have responded to standard first-line treatment. Lefitolimod is subsequently administered subcutaneously 60 mg twice weekly as maintenance therapy. The primary endpoint is overall survival and secondary study endpoints include progression-free survival, safety and tolerability, as well as Quality of Life (QoL).

The study is conducted in collaboration with three highly profiled national collaborative study groups: Arbeitsgemeinschaft Internistische Onkologie (AIO) in Germany, Grupo Español de Tratamiento de Tumores Digestivos (TTD) in Spain and Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR) in France.

For more information on IMPALA please visit www.clinicaltrials.gov.

On August 5, 2019 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported financial results for the second quarter 2019 and provided an operational update (Press release, Bellicum Pharmaceuticals, AUG 5, 2019, View Source [SID1234538130]).

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"Thus far in 2019, Bellicum has made significant progress in each of its development programs," said Rick Fair, President and Chief Executive Officer of Bellicum Pharmaceuticals. "We presented encouraging interim data at ASCO (Free ASCO Whitepaper) on our BPX-601 GoCAR-T product candidate, advanced towards a Phase 1 study for BPX-603, our dual-switch HER2-targeted GoCAR-T product candidate, and announced that rivo-cel achieved the primary endpoint in its European registrational study. Looking forward, we have strategically prioritized our GoCAR-T programs and plan to enroll these trials to evaluate how our technology may help extend the impact of CAR-T therapies to the treatment of solid tumors."

PROGRAM HIGHLIGHTS AND CURRENT UPDATES

BPX-601 GoCAR-T

Bellicum presented updated safety and activity data for BPX-601 from a Phase 1/2 study in patients with metastatic pancreatic cancer expressing prostate stem cell antigen (PSCA) at the 2019 American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The data showed a favorable safety profile—with no dose-limiting toxicities—and provided further evidence that GoCAR-T technology boosts expansion and persistence of CAR-T cells in patients. Of 13 patients evaluable for efficacy treated with BPX-601 and a single dose of rimiducid, 8 patients (62%) achieved stable disease, including 3 with tumor shrinkage of 10% to 24%. As a next step in the study, Bellicum is currently enrolling an additional cohort to evaluate repeat rimiducid dosing to re-activate iMC over time, which is intended to deepen and extend the treatment effect. Initial results from this cohort are expected in late 2019 or early 2020.
Controllable Dual-Switch GoCAR-T Product Candidates

Bellicum believes that its next-generation dual-switch GoCAR-T technology may enhance efficacy relative to current generation CAR-T therapy through iMC activation while enabling clinicians to manage certain treatment-emergent toxicities with CaspaCIDe. The company expects IND clearance for BPX-603, a dual-switch GoCAR-T targeting HER2-expressing solid tumors, later this year. The company also expects to submit an IND application for BPX-802, a dual-switch GoCAR-T product candidate targeting an antigen expressed in hematological malignancies.
Rivo-cel

In July, the company announced that rivo-cel achieved the primary endpoint (Event Free Survival at 180 days) and all secondary endpoints in its BP-004 European registrational trial. Data from this trial is expected to form the basis of anticipated submissions of European Marketing Authorisation Applications (MAAs) for rivo-cel and rimiducid in support of potential regulatory approval. The company is actively seeking a partnership for the continued development and commercialization of rivo-cel.
Second Quarter 2019 Financial Results

Cash Position and Guidance: Bellicum reported cash, restricted cash and investments totaling $60.6 million as of June 30, 2019, compared to $98.0 million at December 31, 2018. Based on current operating plans, Bellicum expects that current cash resources will be sufficient to meet operating requirements through at least the end of 2019. During the second quarter, Bellicum utilized its at-the-market financing facility selling 1.2 million shares for net cash proceeds of $4.4 million.

R&D Expenses: Research and development (R&D) expenses were $19.9 million for the second quarter of 2019, compared to $18.4 million for the second quarter of 2018. The higher expenses in the second quarter of 2019 resulted primarily from higher expenditures related to the GoCAR-T platform including initiation of additional clinical sites and costs related to IND filing. R&D expenses for the six months ended June 30, 2019 were $36.7 million compared to $34.9 million for the comparable period in the prior year.

G&A Expenses: General and administrative (G&A) expenses were $7.5 million for the second quarter of 2019 compared to $5.4 million during the comparable period in 2018. The higher expenses in the second quarter 2019 relative to the comparable period in 2018 were primarily due to increased personnel related costs and commercialization preparation activities. G&A expenses for the six months ended June 30, 2019 were $15.1 million compared to $11.1 million for the first six months of 2018.

Net Loss: Bellicum reported a net loss of $26.9 million for the second quarter of 2019 compared to a net loss of $24.2 million for the second quarter of 2018. The results included non-cash, share-based compensation charges of $2.0 million and $3.6 million for the second quarter of 2019 and 2018, respectively. Net loss for the six months ended June 30, 2019 was $51.5 million compared to a loss of $47.0 million for the six months ended June 30, 2018.

Shares Outstanding: At July 31, 2019, Bellicum had 46,254,163 shares of common stock outstanding.

About BPX-601

BPX-601, the company’s first GoCAR-T product candidate, incorporates iMC, Bellicum’s inducible co-activation domain. iMC (inducible MyD88/CD40) is designed to provide a powerful boost to T cell proliferation and persistence and enable the CAR-T to override key immune inhibitory mechanisms, including PD-1 and TGF-beta. BPX-601 is being evaluated as a treatment for solid tumors expressing prostate stem cell antigen (PSCA), including pancreatic, gastric, and prostate cancers.

About Rivo-cel (BPX-501)

Rivo-celTM (rivogenlecleucel) is an allogeneic polyclonal T cell product designed to reduce the rate of relapse of leukemia following a stem cell transplant. The cell treatment contains a diverse repertoire of T cells, which may contribute to a robust graft vs. leukemia effect. Rivo-cel’s antiviral benefits may also reduce morbidity and mortality in patients susceptible to infection following a transplant. The product’s CaspaCIDe safety switch enables this approach by allowing physicians to reduce the number of alloreactive cells in the event of uncontrolled GvHD. Rivo-cel addresses a major unmet need in adult and pediatric leukemia, lymphoma and genetic blood disease patients following a haploidentical stem cell transplant.

On August 5, 2019 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops and commercializes high quality medicines, reported the signing of a collaboration agreement with Shenogen Pharma Group Ltd. ("Shenogen") to evaluate the combination therapy of Innovent’s Tyvyt (generic name: sintilimab injection), a fully human anti-programmed cell death protein 1 (anti-PD-1) monoclonal antibody with Shenogen’s SNG1005, in patients with advanced cancer (Press release, Innovent Biologics, AUG 5, 2019, View Source [SID1234538146]).

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SNG1005 is a conjugate of angiopep-2 and paclitaxel that Shenogen licensed from overseas. Multiple Phase II clinical trials have been completed in the United States (U.S.), and its Phase III clinical trial protocol has been approved by the U.S. Food and Drug Administration (FDA). Shenogen has the full development and commercialization rights for SNG1005 in Greater China. Currently, the Investigational New Drug (IND) application of Phase II/III clinical trial for the treatment of breast cancer carcinoma brain metastases (BCBS) in China has been approved by the National Medical Products Administration (NMPA), and the clinical trial is planned. Tyvyt (sintilimab Injection) is the anti-PD-1 inhibitor co-developed by Innovent and Eli Lilly and Company (Lilly). On 24 December 2018, Tyvyt (sintilimab Injection) was granted approval for market authorization by the NMPA for the treatment of patients with classical Hodgkin’s lymphoma (cHL) that has relapsed or refractory (r/r) after two or more lines of systemic chemotherapy (r/r cHL).

Dr. Kun Meng, Chairman of Shenogen, commented, "The combined therapy of immune check point inhibitors and anti-tumor therapeutics has become the standard approach for the development of anti-tumor treatments. We are looking forward to close cooperation with Innovent in exploring the potential efficacy of anti-PD-1 inhibitor in combination with SNG1005. We are expecting the underlying synergistic effect in various cancers."

"SNG1005 is a first-in-class nab-paclitaxel therapeutic in development that can pass through blood-brain barrier (BBB), and we are very pleased to cooperate with Shenogen to explore the clinical synergistic efficacy with our PD-1 inhibitor. We hope to bring more clinical benefits to patients with advanced carcinomas," said Dr. Hui Zhou, Vice President and Head of Oncology Strategy and Medical Sciences of Innovent.

About SNG1005

SNG1005, a conjugate of angiopep-2 and paclitaxel, binds to the low-density lipoprotein receptor-related protein 1 (LRP1). LRP1 is abundantly expressed on the Blood Brain Barrier (BBB), which facilitates efficient transcytosis movement of paclitaxel across the BBB. Besides its systemic effects, it can specially pass through the BBB and reach brain lesions.

About Tyvyt (sintilimab injection)

Tyvyt (sintilimab injection) is an innovative drug jointly developed in China by Innovent and Eli Lilly and Company. Innovent is also conducting clinical studies of sintilimab injection in the United States. Tyvyt (sintilimab injection) is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1/ PD-1 Ligand-1 (PD-L1) pathway and reactivates T-cells to kill cancer cells. Tyvyt (sintilimab injection) is the only PD-1 antibody in China branded by both a local biopharmaceutical company and a global pharmaceutical company. Tyvyt (sintilimab injection) has been granted marketing approval by the National Medical Products Administration (NMPA) for relapsed or refractory classical Hodgkin’s lymphoma (r/r cHL) and has been included in the 2019 Guidelines of Chinese Society of Clinical Oncology (CSCO) for Lymphoid Malignancies. There are currently more than twenty clinical studies using sintilimab injection, including eight registration studies that evaluate the efficacy of sintilimab injection in other solid tumors.

On August 5, 2019 Eagle Pharmaceuticals, Inc. ("Eagle" or the "Company") (Nasdaq: EGRX) reported a clinical development plan to support the submission of a New Drug Application (NDA) for the Company’s innovative fulvestrant formulation (Press release, Eagle Pharmaceuticals, AUG 5, 2019, View Source [SID1234538131]). Fulvestrant, an estrogen receptor antagonist with no agonist properties, is approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced hormone-related breast cancers. The therapeutic effect of fulvestrant relies on its ability to inhibit estrogen receptors (ER) in cancer cells by binding to and downregulating, or blocking, the ER in breast cancer cells. Recent studies have shown that higher residual ER availability is associated with early disease progression.

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Eagle’s original formulation of fulvestrant was studied in a clinical trial conducted in 2018 in healthy post-menopausal women. The study was conducted in 600 subjects over 140 days; 300 subjects received the branded product FASLODEX and 300 subjects received Eagle’s formulation. A detailed review of the study data led to the hypothesis that the unique properties of Eagle’s formulation would potentially allow for greater inhibition of estrogen receptors. Based on this hypothesis, Eagle has recently completed additional work designed to further enhance its proprietary drug formulation.

In March and June 2019, Eagle met with the FDA and mutually agreed to a clinical program that could provide an efficient approval pathway for the Company’s fulvestrant formulation. The main goal of the clinical research program is to determine if the unique properties of Eagle’s fulvestrant formulation will result in greater inhibition of estrogen receptors, potentially leading to improved efficacy outcomes, including lower disease progression rates, compared to current treatment options.

Eagle intends to begin a pilot study shortly in healthy female volunteers to evaluate the pharmacokinetics and safety of its novel formulation. Once the pilot study results are reviewed, a clinical pivotal trial designed to evaluate fulvestrant exposure and estrogen receptor inhibition based upon the parameters determined with the FDA will be conducted in a target patient population. Depending on recruitment rates and other factors, Eagle believes the pivotal study could be completed within approximately 12 months of commencing enrollment.

"The opportunity to develop a new treatment option that has the potential to better address the epidemic of breast cancer affecting millions of women in the U.S. and worldwide is an important priority for Eagle. Following a thorough review of the data from our previous study, we believe that our fulvestrant product has a unique profile that may allow it to achieve a greater level of estrogen receptor inhibition, and we are encouraged by the guidance provided by FDA to develop a clinical path to further explore the potential of our novel formulation. If successful, the Eagle product could provide a meaningful improvement and a new option to treat this breast cancer patient population," stated Scott Tarriff, Chief Executive Officer of Eagle Pharmaceuticals.

Breast cancer is the most commonly diagnosed cancer in women, with more than 2.8 million breast cancer survivors in the U.S. today; approximately 290,000 women are diagnosed in the U.S. annually. Hormone receptor-positive (HR+) breast cancer is the most common clinical subtype, with the estrogen receptor (ER) being expressed in approximately 70% of those diagnosed.

About Fulvestrant

Fulvestrant is indicated as a monotherapy treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy, or as a combination therapy for the treatment of: (1) HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine based therapy or following disease progression on endocrine therapy, or (2) HR-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy.

On August 5, 2019 Arcadia Biosciences, Inc. (Nasdaq: RKDA), a leader in science-based approaches to enhancing the quality and nutritional value of crops and food ingredients, reported its plan to release its second-quarter 2019 financial and business results after market close on August 14, 2019 (Press release, Arcadia Biosciences, AUG 5, 2019, View Source [SID1234538147]).

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The company has scheduled a conference call for 4:30 p.m. Eastern time (1:30 p.m. Pacific time) to discuss second-quarter results and the quarter’s key strategic achievements.

Interested participants can join the conference call using the following numbers:

U.S. Toll-Free Dial-In:

+1-844-243-4690

International Dial-In:

+1-225-283-0138

Passcode:

1488315

A live webcast of the conference call will be available in the Investors section of Arcadia’s website at www.arcadiabio.com. Following completion of the call, a recorded replay will be available on the company’s investor website.