On October 18, 2017 Moleculin Biotech, Inc., (NASDAQ: MBRX) (“Moleculin” or the “Company”), a clinical stage pharmaceutical company focused on the development of anti-cancer drug candidates, some of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported that 14 qualified cancer clinics have requested to participate in its clinical trial to study Annamycin for the treatment of relapsed or refractory acute myeloid leukemia (“AML”) (Press release, Moleculin, OCT 18, 2017, View Source [SID1234521006]).

“We’ve had a very positive response from the hematology oncology community,” commented Walter Klemp, Chairman and CEO of Moleculin. “With little to no cardiotoxicity and a structure that has been shown to avoid the multidrug resistance mechanisms that often defeat the current first line standard of care for AML, a number of clinicians recognize that Annamycin could provide a second chance to patients who have run out of options.”
Mr. Klemp continued: “We are pleased to have so many sites express interest in this trial, as it should help improve our chances for timely patient recruitment. In addition, seven of these interested sites are in Poland where we believe we will have access to a higher percentage of patients who are what we call ‘treatment naive’, meaning they have not been subjected to any experimental therapies before entering our trial.

On October 18, 2017 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported top-line overall response rate (ORR) results from the independent review committee assessment of the larotrectinib dataset (Press release, Loxo Oncology, OCT 18, 2017, View Source [SID1234521005]). The full dataset is being reserved for a future publication. Consistent with prior guidance, Loxo Oncology expects to submit a New Drug Application (NDA) for evaluation by the U.S. Food and Drug Administration (FDA) in late 2017 or early 2018, and a Marketing Authorisation Application (MAA) for evaluation by the European Medicines Agency (EMA) in 2018.

“Today’s results have exceeded our expectations, and confirm the depth and breadth of response larotrectinib delivers to patients with TRK fusion cancers,” said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. “We are indebted to our investigators and team members, whose care and sophistication in the execution of the larotrectinib clinical development program have now been validated by independent review.”

The following table compares response determinations between the independent review committee and investigators, using a July 17, 2017 data cut-off date:

Independent Review
Committee Assessed
Response (n=55) Investigator Assessed
Response
(n=55)
Overall Response Rate
(ORR = PR+CR) 75%
(95% CI: 61% – 85%) 80%*
(95% CI: 67% – 90%)
Partial Response (PR) 62 % 64%*
Complete Response (CR) 13 % 16 %
Stable Disease 13 % 9 %
Progressive Disease 9 % 11 %
Not Evaluable 4 % 0 %
* Includes one unconfirmed partial response, as of July 17, 2017, which was subsequently confirmed.

Consistent with global written regulatory correspondence, the NDA/MAA dataset includes adult and pediatric tropomyosin receptor kinase (TRK) fusion patients enrolled in Loxo Oncology’s Phase 1 adult trial, Phase 2 trial (NAVIGATE), and Phase 1/2 pediatric trial (SCOUT). The dataset is based on the intent to treat (ITT) principle, using the first 55 TRK fusion patients with RECIST-evaluable disease enrolled to the three clinical trials, regardless of prior therapy or tumor tissue diagnostic method. The primary endpoint for the integrated analysis of efficacy is overall response rate (ORR) according to the independent review committee assessment, as measured by RECIST v1.1. A key secondary endpoint is ORR according to local investigator assessment, as measured by RECIST v1.1.

The larotrectinib adverse event profile is consistent with data previously presented publicly.

The larotrectinib program has continued to enroll and treat newly identified patients with TRK fusion cancers, beyond the 55 patients described above. The anti-tumor activity and safety of larotrectinib in these additional patients are consistent with data reported today and previously. Notably, no new patients with CNS metastases have been identified or treated in any setting.

About Larotrectinib (LOXO-101)
Larotrectinib is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In an analysis of 55 RECIST-evaluable TRK fusion adult and pediatric patients, larotrectinib demonstrated a 75 percent independently-reviewed confirmed overall response rate (ORR) and an 80 percent investigator-assessed confirmed ORR, across many different types of solid tumors. Larotrectinib has been granted Breakthrough Therapy Designation Rare Pediatric Disease Designation and Orphan Drug Designation by the U.S. FDA. For additional information about the larotrectinib clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or visit www.loxooncologytrials.com.

About TRK Fusion Cancer
TRK fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1, NTRK2, NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6, LMNA, TPM3). This abnormality results in uncontrolled TRK signaling that can lead to cancer. TRK fusions occur rarely but broadly in various adult and pediatric solid tumors, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, GIST, infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas. TRK fusions can be identified through various diagnostic tests, including targeted next-generation sequencing (NGS), immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescent in situ hybridization (FISH). For more information, please visit www.TRKtesting.com.

On October 18, 2017 Eli Lilly and Company (NYSE: LLY) and CureVac AG reported a global immuno-oncology collaboration focused on the development and commercialization of up to five potential cancer vaccine products based on CureVac’s proprietary RNActive technology (Press release, Eli Lilly, OCT 18, 2017, View Source [SID1234521004]). The companies will use messenger RNA (mRNA) technology that targets tumor neoantigens for a more robust anti-cancer immune response.

“We are excited to be collaborating with CureVac to discover what could potentially be the next frontier of cancer medicines,” said Greg Plowman, M.D., Ph.D., vice president of oncology research at Lilly. “This collaboration reinforces Lilly’s commitment to delivering life-changing medicines to treat and cure people living with cancer around the world.”

Ingmar Hoerr, Ph.D., co-founder and CEO of CureVac, stated, “This new collaboration with Lilly is a testimony to the progress and sophistication of CureVac’s RNActive technology and the potential of mRNA-based therapeutics. We now have the opportunity to combine forces to further expand the exciting space of immuno-oncology with the next generation of cancer therapies. We are thrilled to work with the Lilly team and hope to advance this new treatment paradigm into the clinic and ultimately to the market.”

Under the terms of the agreement, CureVac will receive an upfront payment of $50 million and an equity investment of €45 million. CureVac is also eligible to receive more than $1.7 billion in development and commercialization milestones if all five vaccines are successfully developed, plus tiered royalties on product sales. Lilly is responsible for target identification, clinical development and commercialization. CureVac will be responsible for mRNA design, formulation and manufacturing of clinical supply and retains the option to co-promote the vaccine products in Germany.

CureVac’s proprietary RNActive technology will be used to deliver mRNA that ultimately directs the human immune system to target the encoded neoantigens. These tumor-specific neoantigens instruct the patient’s existing immune system to mount a selective and potent response to eradicate the cancer.

This transaction is subject to clearance under the Hart-Scott-Rodino Antitrust Improvements Act and other customary closing conditions. Subject to the closing of this transaction, Lilly expects to incur an acquired in-process research and development charge to earnings of approximately $0.03 per share.

On October 18, 2017 Celsion Corporation (NASDAQ:CLSN), an oncology drug development company, today provided a summary of GEN-1 immunotherapy-related presentations made during the Company’s Research and Development (R&D) Day held on Thursday, October 12, 2017 (Press release, Celsion, OCT 18, 2017, View Source [SID1234521003]). This summary is intended to provide easy access to pertinent, top line information discussed during the conference. A complete webcast of the presentations are available on Celsion’s website at www.celsion.com under the heading News & Investors / Financial Events / Featured Events – October 12, 2017 – Celsion to Host Research and Development Update.

The GEN-1 immunotherapy presentations focused on the Company’s clinical and translational research data from its OVATION Study, a Phase Ib dose escalating clinical trial combining GEN-1, the Company’s DNA-based immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with advanced Stage III/IV ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery. GEN-1 is an interleukin-IL-12 (IL-12) DNA plasmid vector formulated as a nanoparticle in a non-viral delivery system to cause the sustained local production and secretion of the IL-12 protein loco-regionally at the tumor site. The lead clinical investigator for the OVATION Study and leading immuno-oncology experts from the Roswell Park Cancer Institute presented their current experience with GEN-1 immunotherapy for the treatment of ovarian cancer.

Khursheed Anwer, Ph.D., Celsion’s Executive Vice President & Chief Scientific Officer, presented the following:
GEN-1 immunotherapy is a powerful pro-immune modulator designed to modulate the tumor microenvironment through the delivery of the potent immune agent IL-12 into the peritoneal cavity in a local and persistent manner.
IL-12 shifts the tumor microenvironment from immune suppressive to immune activation.
GEN-1 immunotherapy results in the loco-regional production of the potent cytokine IL-12 avoiding toxicities and poor pharmacokinetics associated with systemic recombinant IL-12 protein; lasts up to one week; Dosing can be repeated making GEN-1 immunotherapy ideal for long-term maintenance therapy.

Premal H. Thaker, M.D., Associate Professor in Gynecologic Oncology, Washington University School of Medicine, St. Louis, Missouri presented the final clinical data from the Phase Ib dose-escalating OVATION Study:
Neoadjuvant treatment approach to ovarian cancer has been gaining greater support over the last few years due to safety benefits; Addition of GEN-1 to neoadjuvant chemotherapy was safe and well tolerated.
The R0 margin negative resection score in 64% of patients treated in the OVATION Study appeared to be higher than what you see with neoadjuvant chemotherapy alone; R0 score of 100% in the highest dose group is impressive.

Progression Free Survival (PFS) of over 14 months in the as-treated patient population is on a positive trend since only 2 out of 16 patients have progressed to-date.
The patient population in the OVATION Study was highly advanced (94% at Stage IIIC – IV); better results are anticipated in a mixed population trial.

Richard C. Koya, M.D., Ph.D., Associate Professor of Oncology and Immunology, Director of the Vector Development & Production Facility, Associate Director of the Center for Immunotherapy, Roswell Park Cancer Institute, Center for Immunotherapy, Buffalo, NY presented the following translational research data from the OVATION Study:

GEN-1 treatment when administered in combination with standard of care increased the levels of immune-stimulatory cytokines and tumor infiltrating lymphocytes in a manner that is consistent with the known actions of IL-12.
There is evidence of GEN-1 activity on T-cell numbers as well as T-cell function. A dose-dependent increase in IFN-gamma, a strong mediator of immune response, following the treatment is impressive. Significant reduction in angiogenic growth factor, VEGF, is also a good indicator of the IL-12 treatment effect.

The decrease in immune suppressive signals and the increase in the ratio of cytotoxic CD8+ cells to immune suppressive signals suggest a shift in tumor environment in favor of immune stimulation. A highly immune suppressive tumor environment is linked with a worsening of the disease and poor treatment outcome. A shift in the tumor microenvironment in favor of immune stimulation following GEN-1 treatment is a positive indication of the IL-12 treatment effect.

The modulation of tumor microenvironment in favor of immune stimulation by GEN-1 raises its potential combination benefits with other forms of immunotherapies, especially adoptive T-cell therapy. GEN-1 pre-treatment has potential to improve the survival and potency of the engineered T-cells, a major limitation in adoptive T-cell therapies.
About the OVATION Study

The Phase Ib trial was designed to evaluate weekly intraperitoneal dosing of GEN-1 in combination with neoadjuvant chemotherapy, the standard of care for patients newly diagnosed with ovarian cancer. Concurrently with neoadjuvant chemotherapy, enrolled patients will receive escalating weekly doses of GEN-1, from levels beginning at 36mg/m², to 47mg/m², 61mg/m² and 79mg/m² weekly for 8 treatments in total, with interval debulking surgery to follow. The regimen was primarily evaluated for its safety and tolerability. GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation.

On October 18, 2017 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported that Genentech, a member of the Roche Group, has commenced a Phase 1b/2 study for the treatment of gastric cancer with BL-8040 in combination with atezolizumab (TECENTRIQ), Genentech’s anti-PDL1 cancer immunotherapy agent (Press release, BioLineRx, OCT 18, 2017, View Source [SID1234521002]).

Up to 40 patients are planned to be enrolled in this multicenter, randomized, controlled, open-label study to evaluate the clinical response, safety and tolerability, as well as multiple pharmacodynamic parameters, of BL-8040 in combination with atezolizumab. Initially, patients will receive BL-8040 injections as priming monotherapy, after which they will receive both BL-8040 and atezolizumab, and continue with multiple treatment cycles for up to two years or, until disease progression, clinical deterioration or unacceptable toxicity.

The clinical study collaboration between BioLineRx and Genentech is part of MORPHEUS, Roche’s novel cancer immunotherapy development platform. MORPHEUS is a phase 1b/2 adaptive platform to develop combinations of cancer immunotherapies more rapidly and efficiently.

Philip Serlin, Chief Executive Officer of BioLineRx, stated, “This is the third trial to commence under our collaboration with Genentech for the combination of our CXCR4 inhibitor lead oncology platform and their anti-PDL1 inhibitor, following initiation of a pancreatic cancer study in July and initiation of an AML study in September. We are therefore hopeful that combining atezolizumab with BL-8040 can lead to a significant advancement in the treatment of gastric cancer, and of other solid tumors that are difficult to treat. BL-8040 has shown to induce robust mobilization of immune cells, improve the infiltration of T cells into solid tumors, and affect the immunosuppressive tumor micro-environment. We look forward to the results of this trial and the initiation of an additional combination study under this collaboration, planned for later this year.”

This study is being carried out as part of BioLineRx’s cancer immunotherapy collaboration with Genentech, which includes several Phase 1b/2 studies investigating BL-8040 in combination with atezolizumab in multiple cancer indications, announced in September 2016.

BL-8040, BioLineRx’s lead oncology platform, is a CXCR4 antagonist that has been shown in clinical trials to be a robust mobilizer of immune cells and to be effective in inducing direct tumor cell death. Additional findings suggest that BL-8040 may be effective in inducing the migration of anti-tumor T cells into the tumor micro-environment, as well as improving the infiltration of T cells into solid tumors. Atezolizumab is a humanized monoclonal antibody designed to bind to PD-L1 in tumor cells and tumor infiltrating immune cells and blocks interactions with the PD-1 and B7.1 receptors. Through this interaction, atezolizumab may enable the activation of T cells, whose migration into the tumor may be enhanced by BL-8040.

About BL-8040

BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and stem cell mobilization. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing cell death (apoptosis). In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.