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.

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"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.

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.

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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.

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]).

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"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.

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".

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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

On March 26, 2019 Arvinas, Inc. (Nasdaq: ARVN), a biopharmaceutical company creating a new class of therapies that degrade disease-causing proteins, reported financial results for the fourth quarter and full year ended December 31, 2018 and provided a corporate update (Press release, Arvinas, MAR 26, 2019, View Source [SID1234534623]).

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"Since our founding in 2013, Arvinas has been focused on leading and advancing the field of targeted protein degradation and we are proud of our progress to date. 2018 was a transition year for Arvinas with preparations for moving into the clinic with our two lead programs. The hard work and dedication of our team recently enabled us to initiate patient dosing in our first Phase 1 clinical trial of ARV-110, our oral androgen receptor (AR)-targeted PROTAC protein degrader for the treatment of men with metastatic castration-resistant prostate cancer," said John Houston, Ph.D., President and CEO of Arvinas. "We believe ARV-110 is the first in this new class of targeted protein degraders to enter human clinical trials, and we anticipate bringing ARV-471, an estrogen receptor (ER)-targeted PROTAC protein degrader for the treatment of women with locally advanced or metastatic ER+ / HER2- breast cancer, into the clinic in the third quarter of 2019."

"While our initial clinical programs will be in oncology, this is just the beginning for Arvinas. There are many protein targets for which our PROTAC technology may be advantageous, including ‘undruggable’ targets. We are moving into new and exciting therapeutic areas, developing new PROTAC protein degraders against neurodegenerative targets such as tau, which is implicated in Alzheimer’s Disease. We have engineered targeted PROTAC protein degraders that, in preclinical studies, have achieved blood-brain barrier penetration, a key step in developing drugs with the potential to treat neurodegenerative diseases," continued Dr. Houston.

Business Highlights and Recent Developments

Initiated patient dosing in the first Phase 1 clinical trial of ARV-110, which will evaluate the safety and tolerability of ARV-110 in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on standard of care therapies. Arvinas believes ARV-110 is the first in a new class of targeted protein degraders to enter human clinical trials and anticipates preliminary data from the study in the second half of 2019.
Completed an initial public offering ("IPO") in October 2018, issuing an aggregate of 7,700,482 shares of common stock, including 200,482 additional shares of common stock upon the exercise in part by the underwriters of their option to purchase additional shares at a public offering price of $16.00 per share, for aggregate gross proceeds of approximately $123.2 million.
Closed a $55 million Series C financing in March 2018. The financing was led by new investor Nextech Invest, with participation from additional new investors Deerfield Management, and Hillhouse Capital. All existing investors also participated in this financing round, including Canaan Partners, 5AM Ventures, RA Capital Management, OrbiMed, and New Leaf Venture Partners.
Presented positive preclinical data, at the 2018 San Antonio Breast Cancer Symposium (SABCS) on ARV-471, a PROTAC protein degrader for the degradation of the estrogen receptor (ER), which demonstrated:

Potent ER degradation in wild-type and mutant ER-expressing cell lines
Tumor shrinkage after oral administration in an orthotopic MCF7 breast cancer xenograft model, accompanied by near-complete ER degradation
More robust tumor growth inhibition and ER degradation compared to fulvestrant, a standard of care agent
Significant tumor regressions when combined with a CDK4/6 inhibitor and overall superior anti-tumor activity when compared to the combination of fulvestrant and a CDK4/6 inhibitor
Tumor growth inhibition of tamoxifen-resistant and ER gene (ESR1) mutant tumors while also reducing tumor ER levels
No ER agonist activity
Anticipated Milestones and Expectations

Disclose preliminary data from the Phase 1 clinical trial of ARV-110 in the second half of 2019.
Initiate a Phase 1 clinical trial of ARV-471 in women with locally advanced or metastatic ER+ positive / HER2- negative breast cancer in the third quarter of 2019 and collect preliminary clinical data in 2020.
Present preclinical data from our tau program in the second half of 2019.
Financial Guidance

Based on its current operating plan, Arvinas expects its cash, cash equivalents, and marketable securities as of December 31, 2018 will be sufficient to fund its operating expenses and capital expenditure requirements into the first half of 2021.

Full Year and Fourth Quarter Financial Highlights

Cash, Cash Equivalents and Marketable Securities Position: As of December 31, 2018, cash, cash equivalents, and marketable securities were $187.8 million as compared to $39.2 million as of December 31, 2017. The increase related to net proceeds from our IPO of $114.6 million, proceeds from our Series C financing of $55.0 million, proceeds from our Pfizer collaboration of $28.0 million, and proceeds from a partially forgivable loan of $2.0 million; offset by cash used to fund operations and professional fees paid related to our IPO of $51.0 million. Cash, cash equivalents, and marketable securities increased by $98.0 million in the fourth quarter of 2018. This increase related to net proceeds from our IPO of $114.6 million, offset by cash used to fund operations, and professional fees paid related to our IPO of $16.6 million.

Research and Development Expenses: Research and development expenses were $45.2 million and $14.6 million for the year and quarter ended December 31, 2018, respectively as compared to $28.8 million and $6.7 million for the year and quarter ended December 31, 2017, respectively. The increase in research and development expenses for the year and quarter primarily related to investigational new drug application ("IND")-enabling costs associated with ARV-110 and ARV-471 in addition to increases in costs associated with our discovery operations.

General and Administrative Expenses: General and administrative expenses were $12.9 million and $5.8 million for the year and quarter ended December 31, 2018, respectively as compared to $3.5 million and $1.2 million for the year and quarter ended December 31, 2017, respectively. The increase in general and administrative expenses for the year and quarter primarily relate to increases in our infrastructure in preparation of becoming a publicly traded company.

Revenues: Revenue was $14.3 million and $3.4 million for the year and quarter ended December 31, 2018, respectively as compared to $7.6 million and $2.6 million for the year and quarter ended December 31, 2017, respectively. This increase in the year and quarter was due to an increase in license and rights to technology and research and development activities primarily related to the Pfizer collaboration agreement initiated in January 2018 and the expanded Genentech agreement that was initiated in November 2017.

Net Loss: Net loss was $41.5 million and $16.1 million for the year and quarter ended December 31, 2018, respectively as compared to $24.0 million and $4.7 million for the year and quarter ended December 31, 2017, respectively. The increase in net loss for the year and quarter ended December 31, 2018 was primarily due to the progression of ARV-110 through IND-enabling activities, clinical trial start-up costs for ARV-110, the initiation of IND-enabling activities for ARV-471, investments in our discovery programs and investments in our infrastructure in preparation for becoming a publicly traded company offset by an increase in revenue primarily related to the expanded Genentech collaboration agreement initiated in November 2017 and the Pfizer collaboration agreement initiated in January 2018.

About ARV-110
ARV-110 is an orally-bioavailable PROTAC protein degrader designed to selectively target and degrade androgen receptor (AR). ARV-110 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer (mCRPC). ARV-110 has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies. Arvinas believes the differentiated pharmacology of ARV-110, including its iterative activity, has the potential to translate into improved clinical outcomes for patients.

About ARV-471
ARV-471 is targeting the estrogen receptor (ER) for the treatment of women with locally advanced or metastatic ER+ / HER2- breast cancer. A Phase 1 clinical trial for ARV-471 in women with locally advanced or metastatic ER+ positive / HER2- negative breast cancer, is expected to begin in the third quarter of 2019 and preliminary clinical data is expected in 2020.