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Small Molecule Drug – ETC-206 – A Novel, Highly Selective Anti-Cancer Drug – Acquired By AUM Biosciences

On December 4, 2018 AUM Biosciences (AUM), a Singapore headquartered oncology-focused biotechnology company, reported that it has licensed its first novel, highly selective anti-cancer drug, ETC-206, from A*STAR’s Experimental Therapeutics Centre (ETC) (Press release, AUM BioSciences, DEC 4, 2018, View Source [SID1234533612]). The Agency for Science, Technology and Research (A*STAR) is Singapore’s lead public sector agency that spearheads economic oriented research to advance scientific discovery and develop innovative technology.

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AUM has licensed the global rights to develop, commercialize and manufacture ETC-206 in all indications. ETC-206 was discovered and developed through a collaboration between A*STAR’s Experimental Therapeutics Centre (ETC) and Duke-NUS Medical School (a partnership between Duke University School of Medicine and the National University of Singapore). It advanced into first-in-man trials in December 2016. Initial clinical studies suggest that ETC-206 is very well tolerated and could be used as a thera∂ßpy across a range of liquid and solid tumor types.

The drug promises a more targeted approach by inhibiting the Mnk enzyme in cancer cells, which is a key player in promoting cancer growth when activated. This could lower mortality rates for cancer and improve quality of life for cancer patients compared to traditional chemotherapy, which kills cells in a less specific fashion and affects more than just the cancer cells.

"Due to low efficacy and steep costs associated with many cancer treatments, the demand for more precise anti-cancer treatments has become imperative. AUM’s small molecule and biomarker driven approach allows us to implement innovative trial designs enabling "multiple shots on goal", in cancer treatment," AUM’s Chief Executive Officer, Mr. Vishal Doshi said.

ETC-206 is the first in AUM’s pipeline of novel targeted therapies with the potential to be developed both independently and in combination with other therapies. The drug’s ability to isolate and target only cancerous cells promises a breakthrough opportunity globally.

"ETC-206 is a prime example of how A*STAR has been able to translate R&D into positive outcomes to create economic growth and enhance lives for Singaporeans. We look forward to working closely with more Singapore based enterprises such as AUM Biosciences as we continue to leverage our drug discovery and development capabilities to support the growth of the local biotech ecosystem in Singapore." Said Dr Damian O’Connell, Chief Executive Officer of A*STAR’s Experimental Therapeutics Centre.

"Duke-NUS scientists and researchers have led many discoveries with great potential for the welfare of people in Singapore and beyond," stated Dr. David Epstein, Director of Duke-NUS’ Centre for Technology and Development (CTeD), and the School’s Vice Dean for Innovation and Entrepreneurship, who is also an associate professor of the Cancer and Stem Cell Biology Programme. "ETC-206 is an important accomplishment exemplifying Duke-NUS’s mission of facilitating the translation of basic research into commercial entities and products. We are proud to partner with A*STAR in realizing this enterprising venture that was ‘Made in Singapore’ and is being taken forward by AUM, a Singapore-based startup. We look forward to more startups creating entrepreneurship opportunities in the sector."

ETC-206’s licensing by AUM not only puts Singapore on the map, but also enables the company to be at the forefront of emerging oncology trends. This is a significant step towards its vision of "Asia to global" by accelerating the development of innovative and affordable medicines.

"We are now speaking with investors to accelerate ETC-206’s development and our broader molecule acquisition roadmap. AUM will fund further clinical development and will be responsible for regulatory filings, and for clinical studies for this and future drugs," Mr. Doshi commented.

As a future roadmap, AUM has a strategic focus of acquiring and developing promising small molecules targeted oncology assets to unlock their potential, including those that are de-prioritized or not progressed by their originators due to strategic and financial limitations in the healthcare industry. Its mandate of "No biomarker, No drug" serves to increase the probability of success.

Cancer prevalence in Asia is estimated at 17.4 million in 2018, with about 8.8 million new cases every year, accounting for about half of the new global cancer cases. The number of new cases in Asia is expected to increase from 8.8 million in 2018 to 11.8 million by 2030 creating a huge unmet medical need in Asia.

TG Therapeutics, Inc. Announces Follow-Up Data from the Triple Combination of Ublituximab, Umbralisib, and Bendamustine in Patients with DLBCL and FL at 60th American Society of Hematology Annual Meeting and Exposition

On December 4, 2018 TG Therapeutics, Inc. (NASDAQ: TGTX), reported updated clinical data from its Phase I/Ib trial of ublituximab (TG-1101), the Company’s novel glycoengineered anti-CD20 monoclonal antibody in combination with umbralisib (TGR-1202), the Company’s oral, next generation PI3K delta inhibitor, and bendamustine, in patients with Diffuse Large B-cell Lymphoma (DLBCL) and Follicular Lymphoma (FL) (Press release, TG Therapeutics, DEC 4, 2018, View Source [SID1234532244]). Data from this trial was presented yesterday evening during a poster session at the 60thAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, "The data presented yesterday further supports our belief that our proprietary U2 combination is an ideal backbone regimen on which to build novel multi-drug combinations. The triple therapy of U2 plus bendamustine is highly active and well tolerated in advanced patients, resulting in durable responses with some patients on study 36+ months." Mr. Weiss continued, "We are looking forward to an exciting 2019, with pivotal data expected from the ongoing UNITY-NHL registration directed program in the first half of the year."

Below summarizes the data from the poster presentation.

Combination of Umbralisib, Ublituximab, and Bendamustine is Safe and Highly Active in Patients with Advanced DLBCL and Follicular Lymphoma (Abstract 4197)

This poster presentation includes data from patients with relapsed or refractory DLBCL or FL treated with the triple combination of umbralisib, ublituximab and bendamustine. Thirty-nine patients were evaluable for safety of which 38 were evaluable for efficacy (one patient discontinued due to a treatment-related adverse event (AE), neutropenia, prior to first efficacy assessment). Twenty-two patients (56%) were refractory to prior treatment. Overall, the triple combination was well tolerated and highly active in patients with advanced indolent and aggressive NHL, including those not eligible for HD/SCT or CD19 CART therapy.

Efficacy highlights from this poster include:

85% (11 of 13) ORR, including a 54% CR rate, observed in patients with relapsed or refractory FL
48% (12 of 25) ORR, including a 36% CR rate, observed in patients with relapsed or refractory DLBCL
PRESENTATION DETAILS:

The above referenced presentation is available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.

Inovio Announces Initiation of Phase 2 Trial in New HPV Indications

On December 4, 2018 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported the dosing of the first patient in a Phase 2 combination trial to evaluate MedImmune’s MEDI0457 (formerly called INO-3112 which MedImmune in-licensed from Inovio) in combination with durvalumab targeting a broad array of cancers associated with the human papilloma virus (HPV) (Press release, Inovio, DEC 4, 2018, View Source [SID1234531968]).

This open-label trial funded by MedImmune, the global biologics research and development arm of AstraZeneca, is sponsored by noted cancer researcher Dr. Michael Frumovitz, MD, MPH, of the MD Anderson Cancer Center in Houston, Texas. MedImmune is evaluating MEDI0457 in combination with durvalumab, an anti-PD-L1 immune checkpoint inhibitor, in patients with HPV-associated cervical, anal, penile, and vulvar cancers in arms of a clinical trial with an estimated total enrollment of 77 patients. For additional information about the study, please visit www.clinicaltrials.gov (search identifier NCT03439085).

The opening of this trial will result in a milestone payment from MedImmune to Inovio. Financial arrangements were not disclosed.

Dr. Frumovitz said, "This is the first Phase 2 clinical trial at MD Anderson that is focused not on the site of disease origin, but instead on the cause of a cancer — in this case exposure to HPV 16 or 18. The HPV Moon Shot at MD Anderson has developed an entire research program with this philosophy in mind — that HPV-associated cancers behave similarly, regardless of site of origin, and should be studied as a whole, not as individual cancers. This study will be "site agnostic", meaning any patient with an HPV 16/18 associated cancer, regardless of primary site, will be eligible. Another truly unique aspect of this study is a separate cohort for patients who are HIV positive with an HPV 16/18 associated cancer."

Dr. J. Joseph Kim, Inovio’s President and Chief Executive Officer, said, "We are pleased to see Inovio’s cancer-fighting immunotherapy, in MEDI0457, expand to new cancer indications. Such expansion is great for patients and the oncology community. For Inovio, amplification of HPV cancer targets holds the potential to bring about additional milestone and royalty payments."

An article in the online edition of Clinical Cancer Research highlights a recent Phase 1 study of MEDI0457 as a monotherapy in 22 HPV-positive patients with HPV-associated head and neck cancer that demonstrated MEDI0457 generated robust HPV16/18 specific CD8+ T cell responses in peripheral blood and increased CD8+ T cell infiltration in resected tumor tissue. One patient in that trial who initially displayed a slight increase in T cell immune responses developed progressive disease at 11 months into the study and subsequently received a PD-1 checkpoint inhibitor. The patient achieved a complete response, which has sustained for over two years and counting. Increasing evidence suggests that response rates from checkpoint inhibitors can be enhanced when used in combination with cancer vaccines like MEDI0457 that generate tumor-specific T cells.

About MEDI0457 and VGX-3100

MEDI0457 (formerly called INO-3112 (VGX-3100, plus IL-12) which MedImmune in-licensed from Inovio) is under evaluation by MedImmune to treat HPV-associated cancers. Inovio is investigating VGX-3100, a DNA-based immunotherapy for the treatment of HPV-16 and HPV-18 infection and pre-cancerous lesions of the cervix (Phase 3) and vulva (Phase 2) and anal (Phase 2). VGX-3100 has the potential to be the first approved treatment for HPV infection of the cervix and the first non-surgical treatment for pre-cancerous cervical lesions. VGX-3100 works by stimulating a specific immune response to HPV-16 and HPV-18, which targets the infection and causes destruction of pre-cancerous cells. In a randomized, double-blind, placebo-controlled Phase 2b study in 167 adult women with histologically documented HPV-16/18 cervical HSIL (CIN2/3), treatment with VGX-3100 resulted in a statistically significantly greater decrease in cervical HSIL and clearance of HPV infection vs. placebo. The most common side effect was injection site pain, and no serious adverse events were reported. VGX-3100 utilizes the patient’s own immune system to clear HPV-16 and HPV-18 infection and pre-cancerous lesions without the increased risks associated with surgery, such as loss of reproductive health and negative psychosocial impacts.

Under the 2015 agreement, MedImmune acquired exclusive rights to Inovio’s INO-3112, now called MEDI0457. MEDI0457 targets cancers caused by HPV types 16 and 18 which are responsible for more than 70 percent of cervical pre-cancers and cancers and are involved in the development of other tumors. Within the broader license and collaboration agreement, MedImmune and Inovio are co-developing one additional DNA-based cancer therapy product not included in Inovio’s current product pipeline, which MedImmune has exclusive rights to develop and commercialize. Inovio will receive development, regulatory and commercialization milestone payments for these additional cancer vaccine products and will be eligible to receive royalties on worldwide net sales.

About Durvalumab

Durvalumab, a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumor’s immune-evading tactics and inducing an immune response. As part of a broad development program, durvalumab is being investigated as monotherapy and in combination with IO, small molecules, and chemotherapies across a range of tumors and stages of disease.

Preliminary Results from Randomized Phase 2 Trial Demonstrate Trilaciclib Improved Progression-Free Survival in Combination with Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer

On December 4, 2018 G1 Therapeutics, Inc. (Nasdaq: GTHX), a clinical-stage oncology company, reported preliminary anti-tumor efficacy and myelopreservation data from its randomized, open-label Phase 2 trial evaluating trilaciclib in combination with chemotherapy as a treatment for metastatic triple-negative breast cancer (mTNBC) (Press release, G1 Therapeutics, DEC 4, 2018, View Source [SID1234531965]). These data will be presented on Wednesday, December 5 at a poster discussion Spotlight Session at the 2018 San Antonio Breast Cancer Symposium (SABCS), being held in San Antonio, Texas.

The poster is now available on the Publications page of the company’s website.

"In settings such as metastatic triple-negative breast cancer where chemotherapy is dosed until disease progression, trilaciclib has the potential to deliver both multi-lineage myelopreservation and anti-tumor efficacy benefits to patients," said Raj Malik, M.D., Chief Medical Officer and Senior Vice President, R&D. "In this trial, we observed promising early progression-free survival results favoring trilaciclib, as well as myelopreservation benefits across neutrophils, red blood cells, platelets, and lymphocytes."

Trial Design

This randomized, open-label Phase 2 clinical trial enrolled 102 patients with mTNBC who had received 0-2 prior lines of therapy in the recurrent/metastatic setting. In this three-arm trial, all patients received a chemotherapy regimen of gemcitabine and carboplatin (GC). Patients were randomized to receive GC only or GC plus one of two dosing schedules of trilaciclib: trilaciclib administered on the day of chemotherapy (GC/Tx1) or trilaciclib administered the day prior to and the day of chemotherapy (GC/Tx2).

Key Trial Findings

Preliminary median progression-free survival (PFS) was 5.4 months in the GC arm, 8.8 months in the GC/Tx1 arm (hazard ratio 0.52, p=0.0669) and 7.3 months in the GC/Tx2 arm (hazard ratio 0.49; p=0.0546). A combined analysis of trilaciclib-treated patients showed PFS of 5.4 months for the GC arm and 7.9 months for trilaciclib (hazard ratio 0.50, p=0.0189).

Preliminary objective response rate (ORR) was 29.2% in the GC arm, 43.3% in the GC/Tx1 arm and 36.7% in the GC/Tx2 arm.

PFS and ORR in the control arm were consistent with historical data1.

Overall survival (OS) data is immature. OS and updated PFS and ORR will be reported when available.

J Clin Oncol 32:3840-3847

Patients in both trilaciclib groups remained on therapy for a longer duration of time compared to GC only (median weeks: GC=14.4; GC/Tx1=20.0 weeks; GC/Tx2=19.0 weeks).

On a per-patient basis, the number of patients experiencing myelosuppression events was similar across the three arms. When adjusted for the duration of chemotherapy, the trial demonstrated that patients receiving trilaciclib experienced multi-lineage myelopreservation benefits.

Consistent with previous trilaciclib Phase 2 trials, treatment was well tolerated with no trilaciclib-related serious adverse events reported.

Poster Information

Title: Trilaciclib (T), a CDK4/6 inhibitor, dosed with gemcitabine (G), carboplatin (C) in metastatic triple negative breast cancer (mTNBC) patients: Preliminary phase 2 results

Abstract Number: 1191

Presentation Number: PD1-01

Session Title: Developmental Therapeutics

Date / Time / Location: December 5, 5-7 p.m. CST/6-8 p.m. EST, Stars at Night Ballroom 1&2, Henry B. Gonzalez Convention Center

Presenter: Joyce O’Shaughnessy, M.D. (Texas Oncology-Baylor Charles A. Sammons Cancer Center)

For more information about the 2018 San Antonio Breast Cancer Symposium, please visit View Source

About Trilaciclib

Trilaciclib is a first-in-class myelopreservation therapy designed to improve outcomes of patients who receive chemotherapy by preserving hematopoietic stem and progenitor cell (HSPC) and immune system function. Trilaciclib is a short-acting intravenous CDK4/6 inhibitor administered prior to chemotherapy.

Trilaciclib is being evaluated in four randomized Phase 2 clinical trials. G1 has reported positive results from three of these trials in 2018. Two trials showed myelopreservation benefits in newly diagnosed, treatment-naive SCLC patients. In the first trial, trilaciclib was administered in combination with a chemotherapy regimen of etoposide and carboplatin (NCT02499770); topline data were released in March and additional data were reported at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress. In the second trial, trilaciclib was administered in combination with the same chemotherapy regimen and the checkpoint inhibitor Tecentriq (atezolizumab) (NCT03041311); topline data were reported in November. Results from a trial in combination with chemotherapy in metastatic triple-negative breast cancer (NCT02978716) showing enhanced progression-free survival and multi-lineage myelopreservation benefits are being presented at the San Antonio Breast Cancer Symposium on December 5, 2018. The company plans to release topline data from a trial in combination with chemotherapy in previously treated SCLC (NCT02514447) by the end of 2018.

LineaRx to Hold Analyst Day Webinar to Announce DNA Vaccine Preclinical Data and Efficacy of In-Licensed CAR T Therapy

On December 4, 2018 LineaRx, Inc., the biotherapeutics company based on the use of large-scale production of gene-sized DNA by Polymerase Chain Reaction ("PCR") and dedicated to revolutionizing biotherapeutics for the masses in affordability, availability, time-to-market, and reducing the risk associated with virally mediated therapy, and a wholly-owned subsidiary of Applied DNA Sciences, Inc. (NASDAQ: APDN), reported that it will host an Analyst Day via webinar on Thursday, December 6, 2018 at 12 p.m. to 1:30 p.m. EST (Press release, Applied DNA Sciences, DEC 4, 2018, View Source [SID1234531906]).

During the 90-minute technical presentation Dr. James Hayward, CEO of LineaRx, Dr. Michael Hogan, Vice President of Life Sciences and Dr. Stephen Hughes, Director of DNA Programs will address:

Collaborative data on PCR-produced anti-cancer (anti-telomerase) vaccine show immunogenicity in mice,
Licensed CAR-T Therapy; partner data to be presented show efficacy in animals and humans when delivered via plasmid and virus, which bodes well for the prospect of similar efficacy of corresponding linear construct under development,
The concept for adoptive cell therapies without delay: "Networked DNA-producing PCR devices informed by Artificial Intelligence and located in hospitals operating under cGMP", and,
Proprietary IP should enable high levels of gene expression, self-transducing genes, transiently expressed genes without genomic integration; the sum of which should generate localized, in-hospital production of more effective adoptive cell therapies, faster, with a higher Therapeutic Index and a simpler mode of manufacture.
LineaRx Webinar Information

To participate in the LineaRx webinar, please follow the instructions below. Management will take questions from select invitees in the Q&A portion of the event.

To Participate:

Participant Toll Free: 1-844-887-9402
Participant Toll: 1-412-317-6798
Please ask to be joined to the LineaRx webinar
Live webcast: View Source
Replay (available 1 hour following the conclusion of the live call through December 13, 2018):

Participant Toll Free: 1-877-344-7529
Participant Toll: 1-412-317-0088
Participant Passcode: 10126911
Webcast replay: View Source
"This Analyst Day webinar serves as an excellent platform from which to build awareness for LineaRx’s competitive advantages and user benefits to the biotherapeutics industry at large. Anyone currently utilizing plasmid DNA and/or virus to transduce cells, in the DNA/RNA vaccine space, involved in CRISPR as well as, CAR-T Therapy could benefit greatly from our technology," stated Dr. Hayward.