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Transgene and BioInvent Extend their Collaboration to Develop Multifunctional Oncolytic Viruses for the Treatment of Solid Tumors

On March 26, 2019 BioInvent International AB (OMXS: BINV), a biotech company focused on the discovery and development of novel immuno-regulatory antibodies to treat cancer and Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of solid tumors, reported the extension of their collaboration to co-develop multi-functional oncolytic viruses (OV) encoding for undisclosed antibodies sequences capable of treating a broad range of solid tumors (Press release, Transgene, MAR 26, 2019, View Source [SID1234534629]).

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Under the terms of the extension agreement, Transgene will contribute its industry-leading OV design and engineering expertise, some non-antibody transgenes, as well as its proprietary engineered vaccinia virus (TK-, RR-) backbone, which forms the basis of its Invir.IO platform. BioInvent will provide its cancer biology and antibody expertise to the collaboration as well as one or more antibodies sequences, generated through its proprietary n-CoDeR/F.I.R.S.T. platforms. Certain sequences for an undisclosed target will be selected for encoding within Transgene’s Invir.IO backbone to create a multi-functional OV.

In November 2018, Transgene and BioInvent presented positive data from their initial collaboration at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). These initial data covered the collaboration’s work on an anti-CTLA-4 antibody-armed oncolytic vaccinia virus, based on Transgene’s proprietary vaccinia virus (TK-, RR-) backbone. This enhanced oncolytic vaccinia virus demonstrated its ability to ensure the expression of BioInvent’s anti-CTLA-4 antibody in the tumor with low systemic exposure. It also showed improved efficacy and a better safety profile when compared to the combination of the antibody and the non-armed corresponding oncolytic virus given individually in pre-clinical models.

Consistent with the initial collaboration, research and development costs as well as revenues and royalties from the multifunctional OVs generated as a result of the new collaboration will be shared 50:50.

Encoding BioInvent’s antibodies sequences in Transgene’s proprietary Invir.IO platform, for a direct expression into the tumor, promises to optimize the efficacy and tolerability of these antibodies. Both Transgene and BioInvent believe that these novel multifunctional OVs could be significantly more effective than co-administering an OV and an antibody together.

Commenting on the agreement, Martin Welschof, CEO of BioInvent, said: "The extension of our collaboration with Transgene opens up further opportunities for both companies to combine their expertise and knowledge to develop antibody oncolytic virus combinations capable of treating a broad range of solid tumors. By leveraging BioInvent’s unique and proprietary n-CoDeR/F.I.R.S.T. platforms, we will be able to develop a number of novel first-in-class antibodies that could be delivered directly into the tumor via Transgene’s vaccinia viral backbone, potentially enhancing their efficacy and improving their side effect profile."

Philippe Archinard, PhD, Chairman and CEO of Transgene, said: "We are pleased to extend the scope of our highly productive collaboration with BioInvent. We believe that the next generation of multi-functional oncolytic viruses expressing BioInvent’s highly targeted immune modulators directly in the tumor micro-environment will deliver much improved overall survival outcomes in patients with solid tumors. This agreement further expands Transgene’s broad portfolio of oncolytic viruses in development, the first of which is expected to enter the clinic in 2020."

Integral Molecular to Present Claudin 6 MAbs, a Therapeutic Asset for Solid Tumors, at Annual AACR Conference

On March 26, 2019 Integral Molecular, the industry leader in discovering antibodies against multipass membrane proteins, reported that it will showcase updated data on its discovery of highly specific Claudin 6 MAbs at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) conference in Atlanta on Monday, April 1 (Press release, Integral Molecular, MAR 26, 2019, View Source [SID1234534628]). Claudin 6 is an established membrane protein target expressed in multiple cancers, including ovarian and gastric tumors, and absent from healthy adult tissues. Until now, the structural complexity of Claudin 6 and its similarity to proteins expressed on healthy tissue have limited its exploitation for targeted oncology therapies.

"There is a strong need for therapeutic monoclonal antibodies that can provide more specific and less toxic treatments for ovarian cancer," said Ross Chambers, VP of Antibody Discovery. "Our lead antibody, isolated using our MPS Antibody Discovery platform, shows best-in-class Claudin 6 specificity. We are currently looking for partners to further develop these exciting assets."

Integral Molecular’s MPS Antibody Discovery platform encompasses a comprehensive technology suite that overcomes the obstacles of working with highly conserved and structurally complex membrane protein targets, like Claudin 6. This suite includes antigen engineering and presentation on Lipoparticles, immunization of divergent species, and the use of B-cell cloning to recover rare antibodies. Integral Molecular is currently isolating MAbs against dozens of membrane protein targets and welcomes antibody licensing opportunities and discovery partnerships.

Evotec and The Mark Foundation for Cancer Research announce strategic collaboration in immuno-oncology

On March 26, 2019 Evotec AG (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) and The Mark Foundation for Cancer Research reported that they have entered into a research collaboration to discover and develop first-in-class therapeutics in oncology (Press release, Evotec, MAR 26, 2019, View Source;announcements/press-releases/p/evotec-and-the-mark-foundation-for-cancer-research-announce-strategic-collaboration-in-immuno-oncology-5793 [SID1234534626]). The collaboration, for an initial period of two years, is based on Evotec’s new proprietary drug discovery platform TargetAlloMod, which is focused on disrupting cell signalling via a novel mechanism of action. This approach is expected to deliver highly potent and more durable treatments for both clinically validated and novel immuno-oncology targets.

The Mark Foundation’s focus of funding highly innovative oncology research and drug discovery is extremely well aligned with Evotec’s mission to exploit novel platforms for the generation of first-in-class and clearly differentiated therapies. Under the terms of the agreement, The Mark Foundation will provide research funding to Evotec. Evotec will in turn be responsible for subsequent partnering of the programmes and/or the platform. The Mark Foundation will use its share of potential financial returns to expand its grant portfolio.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, said: "Evotec is very pleased to partner with The Mark Foundation, who is truly dedicated to accelerating potential cures for cancer by investing into promising new technology platforms and well-differentiated drug discovery projects. The support from The Mark Foundation allows us to engage multiple targets through a novel mechanism of action which is expected to deliver more potent but also more durable drug candidates."

Dr Michele Cleary, Chief Executive Officer of The Mark Foundation, said: "Our partnership with Evotec fits well with our goal of advancing early-stage therapeutic innovation. We are excited about the prospect of expanding the options for targeting some of the most challenging but important molecules in cancer immunology."

No financial details of the collaboration were disclosed.

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About TargetAlloMod
Scientists at Evotec have discovered that for certain extracellular receptors, small molecules can bind allosterically and induce a natural proteolytic cleavage process to shed the ectodomain. This results in the disruption of cell signalling and the shed ectodomain can, in many cases, further act as a sink for the native ligand of the targeted receptor. The TargetAlloMod platform comprises a suite of proprietary assay principles and computational tools to assess and screen extracellular receptor targets for shedding and the induction of shedding by small molecule allosteric modulators. This platform has broad applicability across many therapeutic areas.

Kezar Life Sciences Reports Fourth Quarter and Year End 2018 Financial Results and Provides Business Update

On March 26, 2019 Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage biotechnology company discovering and developing novel small molecule therapeutics to treat unmet needs in autoimmunity and cancer, reported its fourth quarter and full year 2018 financial results and business highlights (Press release, Kezar Life Sciences, MAR 26, 2019, View Source [SID1234534625]).

"This past year was pivotal for Kezar, and I’m proud of the tremendous progress our team has accomplished," said John Fowler, Chief Executive Officer. "We successfully completed our IPO, creating a strong capital base, and we are rapidly advancing KZR-616, our first-in-class selective immunoproteasome inhibitor for patients living with severe and underserved autoimmune diseases. We look forward to sharing results from the initial two cohorts from the Phase 1b portion of our trial in lupus patients and initiating our Phase 2 trial in lupus nephritis (LN) in the second quarter of 2019. We are also pleased to announce the planned expansion of our KZR-616 clinical program with additional Phase 2 trials commencing in up to four new indications later this year, including dermatomyositis and polymyositis. Lastly, our ongoing discovery efforts in protein secretion are progressing well, and we anticipate nominating our first oncology clinical candidate before the end of the year."

Fourth Quarter and Recent Clinical and Business Highlights

Our systemic lupus erythematosus (SLE) and LN program is advancing with enrollment continuing in the open-label dose escalation Phase 1b portion in SLE patients. We plan to initiate the Phase 2 portion of the trial in patients with active, proliferative LN and expect to report data from the first two cohorts of the Phase 1b portion in the second quarter of 2019.

We initiated a Phase 1, randomized, double-blind, placebo controlled, single and multiple ascending dose trial to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunomodulatory activity of a new lyophilized formulation of KZR-616. This formulation of KZR-616 has the potential to improve the ease of drug administration, transportation and storage, which we believe may result in increased patient adoption in a commercial setting. Additionally, data from this trial may support development and potential regulatory approval.

Clinical development efforts are underway to initiate trials in up to four additional autoimmune diseases of high unmet need beginning in the second half of 2019, with the first two diseases being dermatomyositis and polymyositis.

The protein secretion program (Sec61 translocon modulation) also advanced during the fourth quarter which will be showcased in two poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Atlanta, GA on April 2, 2019. We remain on track to nominate a first clinical candidate in oncology this year.

Earlier this month, we announced the appointment of Celia Economides as Senior Vice President of Strategy and External Affairs. Ms. Economides will serve as a member of the management team and executive committee leading Kezar’s overall investor relations, communications, patient advocacy and strategic efforts.

Financial Results

Cash, cash equivalents and marketable securities totaled $107.4 million as of December 31, 2018, compared to $51.0 million as of December 31, 2017. The increase in cash, cash equivalents and marketable securities was primarily attributable to IPO proceeds, net of cash used by the Company in operations to advance its clinical stage programs as well as preclinical research and development.

Research and development expenses for the fourth quarter of 2018 increased by $3.0 million to $4.6 million from $1.6 million in the fourth quarter of 2017. Full year R&D expenses increased by $11.7 million in 2018 compared to 2017. This increase was primarily related to advancing both the KZR-616 clinical program across indications and the protein secretion preclinical program in addition to personnel and facility-related expenses.

General and administrative expenses for the fourth quarter of 2018 increased by $1.0 million to $1.8 million from $0.8 million in the fourth quarter of 2017. Full year G&A expenses increased by $4.3 million in 2018 compared to 2017. The increase was primarily due to an increase in stock-based compensation, personnel expenses, consulting and professional fees related to operating as a public company, and facility-related expenses due to the move to our new corporate office.

Net loss for the fourth quarter of 2018 was $5.8 million, or $0.30 per basic and diluted common share, compared to a net loss of $2.3 million, or $3.34 per basic and diluted common share, for the fourth quarter of 2017. Net loss for 2018 was $23.2 million, or $2.26 per basic and diluted common share, compared to $8.5 million, or $14.21 per basic and diluted common share, in 2017.

Total shares outstanding were 19.1 million as of December 31, 2018. Additionally, there were 2.2 million outstanding options granted to purchase common stock at a $3.80 weighted average exercise price as of December 31, 2018.

Actinium Highlights its Participation at the Upcoming Targeted Alpha Therapy International Symposium with Presentations on its AWE Platform, Clinical Programs and New Source of Ac-225 Isotope

On March 26, 2019 Actinium Pharmaceuticals, Inc. (NYSE American: ATNM), reported that two oral and four poster presentations related to its Ac-225 or Actinium-225 based ARC’s or Antibody Radiation-Conjugates have been accepted for presentation at the 11th Targeted-Alpha-Therapy International Symposium (TAT) being held April 1 – 4, 2019 in Ottawa, Canada (Press release, Actinium Pharmaceuticals, MAR 26, 2019, View Source [SID1234534624]). TAT is a bi-annual global conference which brings together thought leaders in alpha-particle therapy innovation. In addition to the oral and poster presentations, Actinium management will also participate in a panel entitled "The Renaissance of Radio Pharmaceuticals – A Commercial Perspective".

Ac-225 is a potent alpha-particle emitting isotope being utilized in Actinium’s ARC programs for targeted conditioning in the planned pivotal Actimab-MDS trial as well as therapeutic and combination trials such as its Actimab-A Venetoclax combination trials and Actimab-MRD therapeutic trial. Ac-225 is also used in Actinium’s AWE or Antibody Warhead Enabling Technology Platform to support its ongoing collaboration with Astellas Pharma, Inc. and to create next-generation ARC’s. Exemplifying the potential of next-generation ARC’s is the oral presentation highlighting Ac-225 labeled daratumumab (Darzalex, Johnson & Johnson).

Dr. Dale Ludwig, Actinium’s Chief Scientific Officer, said, "Actinium-225 is an isotope with great potential for therapeutic applications given its high energy, short pathlength and 10-day half-life. Due to its highly differentiated properties, we are increasing our research related to targeted Actinium-225 through our AWE platform to continue to drive highly differentiated programs to further expand our pipeline into areas of unmet need. We are excited to have the opportunity to highlight research spanning our clinical programs, novel next-generation ARC’s and preclinical efforts with next generation Ac-225 at this year’s TAT. As a leader in Actinium-225 based ARC’s we are thrilled to be at the forefront of these efforts and are committed to continuing to advance this exciting field."

In addition to highlighting Actinium’s clinical programs and AWE platform, Actinium will present a poster comparing the feasibility of using Ac-225 produced in a high-energy linear proton accelerator by the DOE or U.S. Department of Energy to that of traditional Ac-225 produced in a "thorium cow" or generator. The studies evaluated the feasibility of conjugating or labeling accelerator produced Ac-225 to lintuzumab, an anti-CD33 monoclonal antibody used in Actinium’s CD33 ARC program, and the impact on ARC generation. The DOE’s linear proton accelerator process is in addition to its existing generator-based processes and Actinium’s proprietary process for manufacturing Ac-225 in a cyclotron, the last of which is covered by company patents, know-how and trade secrets.

Sandesh Seth, Actinium’s Chairman and CEO, said, "We are excited to present data from our Ac-225 clinical programs and AWE platform at the preeminent conference focused on targeted alpha-particle therapies. We are committed to bringing important therapies to patients with high unmet needs and feel that Ac-225 has the potential to be an optimal warhead when applied in a targeted manner as we do. We intend to stay at the forefront of innovation with the Ac-225 isotope including ARC development, manufacturing and supply. We look forward to highlighting our capabilities and leadership position in several of these areas at TAT as evidenced by the breath and scope of our participation in several oral, poster and panel sessions."

Details of Actinium’s presentations at TAT are as follows:

Oral Presentations:

Title: Highly Effective Treatment of CD38 Positive Experimental Lymphoma with Actinium-225-Daratumuamb
Sponsored by Actinium Pharmaceuticals, Inc.
Date and Time: Tuesday, April 2, 2019 10:10 AM
Presenter: Wojciech Dawicki, PhD, University of Saskatchewan
Location: Ballroom, Fairmont Chateau Laurier

Title: Targeted Alpha-Particle Therapy for Hematologic Malignancies
Date and Time: Thursday, April 4, 2019 2:00 PM
Presenter: Joseph Jurcic, MD, Columbia University Medical Center
Location: Ballroom, Fairmont Chateau Laurier

Poster Presentations:

Title: Radiolabeling of DOTA-conjugated Lintuzumab with 225Ac: Comparison of Th-229-produced and High-Energy Proton Accelerator-produced 225Ac
Date and Time: Tuesday, April 2, 2019 5:00 – 6:30 PM
Location: Canadian Room, Fairmont Chateau Laurier
Presenter: Dale Ludwig, PhD, Actinium Pharmaceuticals, Inc.
Poster #54

Title: A Phase 2 Study of Actinium-225 (Ac-225-lintuzumab) in Older Patients with Untreated Acute Myeloid Leukemia (AML)
Date and Time: Tuesday, April 2, 2019 5:00 – 6:30 PM
Location: Canadian Room, Fairmont Chateau Laurier
Presenter: Mark Berger, MD, Actinium Pharmaceuticals, Inc.
Poster #61

Title: Dosimetric Impact of Ac-227 in Accelerator-Produced Ac-225
Date and Time: Tuesday, April 2, 2019 5:00 – 6:30 PM
Location: Canadian Room, Fairmont Chateau Laurier
Presenter: George Sgouros, PhD, Johns Hopkins University
Poster #62

Title: Impact of Target Cell Number on Target Cell and Tissue Dose for Antibody-Mediated Delivery of Alpha-Emitters
Date and Time: Tuesday, April 2, 2019 5:00 – 6:30 PM
Location: Canadian Room, Fairmont Chateau Laurier
Presenter: George Sgouros, PhD, Johns Hopkins University
Poster #63

Panel

Title: The Renaissance of Radio Pharmaceuticals – A Commercial Perspective
Date and Time: Tuesday, April 2, 2019 2:25 – 3:05 PM
Location: Ballroom, Fairmont Chateau Laurier