On December 11, 2018 Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) reported financial results for its fiscal 2018 fourth quarter and year ended September 30, 2018 (Press release, Arrowhead Research Corporation, DEC 11, 2018, View Source [SID1234532026]). The company is hosting a conference call at 4:30 p.m. EST to discuss results.

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Conference Call and Webcast Details

Investors may access a live audio webcast on the Company’s website at View Source For analysts that wish to participate in the conference call, please dial 855-215-6159 or 315-625-6887 and provide Conference ID 6744427.

A replay of the webcast will be available on the company’s website approximately two hours after the conclusion of the call and will remain available for 90 days. An audio replay will also be available approximately two hours after the conclusion of the call and will be available for 3 days. To access the audio replay, dial 855-859-2056 or 404-537-3406 and provide Conference ID 6744427.

Selected Fiscal 2018 and Recent Events

Hosted an Analyst R&D Day in September 2017 to highlight the following:

The Targeted RNAi Molecule platform, or TRiMTM, which utilizes ligand-mediated delivery and is designed to enable tissue-specific targeting, while being structurally simple. The TRiMTM platform offers several potential competitive advantages including:

A more sophisticated RNAi trigger selection and screening process that identifies potent sequences rapidly in locations that RNAi competitors may miss

Multiple routes of administration including subcutaneous, intravenous, and inhaled

Faster time to clinical candidates

Optimal pharmacologic activity and long duration-of-effect

Potentially wide safety margins

Simplified manufacturing at reduced cost

And, the promise of taking RNAi to tissues beyond the liver

Presented new clinical data at HEP DART 2017 and EASL 2018 demonstrating up to 5.3 Log10 reduction in HBV s-antigen and a Sustained Host Response in 50% of hepatitis B patients following first generation RNAi therapy, ARC-520, in the 2001 open label extension study

One patient serocleared all viral markers, including HBsAg

Began a Phase 1 study of ARO-AAT, Arrowhead’s second generation subcutaneously administered RNAi therapeutic being developed as a treatment for a rare genetic liver disease associated with alpha-1 antitrypsin deficiency

Began a Phase 1/2 study of ARO-HBV, a third-generation subcutaneously administered RNAi therapeutic candidate being developed as a potential treatment for patients with chronic hepatitis B virus infection

Announced that Amgen had administered the first dose of AMG 890, formerly ARO-LPA, in a Phase 1 clinical study, which earned Arrowhead a $10 million milestone payment

Presented clinical data on ARO-AAT at the Alpha-1 National Education Conference and at the AASLD Liver Meeting 2018 demonstrating:

Three monthly doses of 300 mg ARO-AAT led to reductions in serum alpha-1 antitrypsin to below the level of quantitation in 100% of subjects

Reductions were sustained for greater than 14 weeks indicating that quarterly or less frequent dosing appears feasible

Single and multiple doses of ARO-AAT appeared to be well-tolerated at all doses tested

Presented clinical data on ARO-HBV at the World Gastroenterologists Summit and at the AASLD Liver Meeting 2018 demonstrating:

Mean HBsAg reduction of -1.9 Log10 (-98.7%) with a range of -1.3 Log10 (-95.0%) to -3.8 Log10 (-99.98%)

ARO-HBV appeared to be well-tolerated at monthly doses up to 400 mg

Signed a license agreement with Janssen Pharmaceuticals, Inc., part of the Janssen Pharmaceuticals Companies of Johnson & Johnson, for ARO-HBV and a collaboration agreement for up to three RNAi therapeutic candidates that use our proprietary TRiMTM platform against new targets to be selected by Janssen

The total potential deal value is approximately $3.7 billion plus royalties on commercial sales

Received $175 million as an upfront payment and received $75 million in the form of an equity investment by Johnson & Johnson Innovation – JJDC, Inc., at a price of $23.00 per share of Arrowhead common stock

Hosted an R&D Day in October 2018 to discuss in more detail our emerging pipeline of RNAi therapeutics that leverage the TRiMTM platform

Filed for regulatory clearance to begin a Phase 1 study of ARO-ANG3, an RNAi-based investigational medicine targeting angiopoietin like protein 3 (ANGPTL3) being developed for the treatment of dyslipidemias and metabolic diseases

On December 11, 2018 Alligator Bioscience AB (Nasdaq Stockholm: ATORX) reported that regulatory approvals have been obtained for the first clinical study of ATOR-1015 and patient recruitment can now be initiated. ATOR-1015 is a wholly-owned drug candidate developed for tumor-directed immunotherapy (Press release, Alligator Bioscience, DEC 11, 2018, View Source [SID1234538673]).

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The phase I study is a first-in-human dose-escalation study in up to 53 patients with advanced solid tumor disease at five different clinics across Sweden and Denmark. The primary aim of the study will be to investigate the safety and tolerability of the drug and to identify the recommended dose for subsequent Phase II studies.

"The start of clinical phase I study with ATOR-1015 represents a significant milestone for Alligator. We are first in the world with a new concept, a tumor-localizing bispecific CTLA-4 antibody. While the target is clinically validated, the clinical use of CTLA-4 blocking agents is restricted by severe toxicity. ATOR-1015 may provide a solution through its potential for selective activation of the immune system in the tumor area but not elsewhere in the body. The drug’s preclinical results are very promising, clearly supporting this concept", said Per Norlén, CEO of Alligator Bioscience.

As previously communicated, Alligator has appointed Theradex Oncology, a global contract research organization with extensive expertise in oncology clinical development, to conduct the phase I study.

For further information, please contact:
Cecilia Hofvander, Director Investor Relations & Communications
Phone +46 46 540 82 06
E-mail: [email protected]

This information is such information as Alligator Bioscience AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 8:00 a.m. CET on December 11, 2018.

About ATOR-1015
ATOR-1015 is a next generation CTLA-4 bispecific antibody developed for tumor-directed immunotherapy with increased capability of regulatory T-cell depletion. It is wholly-owned by Alligator. ATOR-1015 binds to two different immune receptors: the checkpoint receptor CTLA-4 and the co-stimulatory receptor OX40. The immune activation is increased in areas where both target molecules are expressed at high levels, notably in the tumor microenvironment, which is believed to reduce adverse immune reactions.

On December 11, 2018 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported the initiation of the triple combination arm of the Phase 2a COMBAT/KEYNOTE-202 study in patients with metastatic pancreatic cancer (PDAC) under its immuno-oncology collaboration with Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside the United States and Canada) (Press release, BioLineRx, DEC 11, 2018, View Source;p=irol-newsArticle&ID=2380207 [SID1234532008]). As previously announced, the triple combination arm will investigate the safety, tolerability and efficacy of BL-8040, KEYTRUDA and chemotherapy.

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The triple combination arm will focus on second-line pancreatic cancer patients, and will include approximately 40 patients with unresectable metastatic pancreatic adenocarcinoma who have progressed following first-line therapy prior to enrollment. Patients will receive BL-8040 monotherapy priming treatment for 5 days, followed by ongoing cycles of the combination of chemotherapy (Onivyde/5-fluorouracil/leucovorin – 5-FU/LV), KEYTRUDA and BL-8040 until progression. The primary endpoint of the study is the objective response rate (ORR) assessed by RECIST v1.1 criteria. Secondary endpoints will include overall survival, progression free survival, and the disease control rate.

"We are pleased to commence this triple combination arm of our Phase 2a pancreatic study, under the framework of our immuno-oncology collaboration with MSD," stated Philip Serlin, Chief Executive Officer of BioLineRx. "We believe that the addition of chemotherapy may be synergistic with BL-8040 and KEYTRUDA, as chemotherapy has been shown to reduce overall tumor burden while inducing immunogenic cell death, leading to activation and expansion of new tumor-reactive T-cells. Based on its mechanism of action, we believe that BL-8040 may facilitate the infiltration of these T-cells into the tumor core, alongside the restoration of T-cell activity within the tumor by KEYTRUDA. We look forward to results of the study expected in the second half of 2019."

At the recent European Society for Medical Oncology 2018 Congress in Munich, Germany, BioLineRx disclosed top-line results from the dual combination arm of the Phase 2a COMBAT/KEYNOTE-202 study, evaluating PDAC patients treated with BL-8040 in combination with KEYTRUDA. The results show encouraging disease control and extended overall survival, particularly in patients undergoing second-line treatment. In addition, the data also demonstrate that BL-8040 significantly improves T-cell infiltration into the tumor and reduces immunosuppression in the tumor microenvironment.

About the COMBAT/KEYNOTE-202 Study

The Phase 2a COMBAT/KEYNOTE-202 study was originally designed as an open-label, multicenter, single-arm trial to evaluate the safety and efficacy of the combination of BL-8040 and KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside the United States and Canada), in over 30 subjects with metastatic pancreatic adenocarcinoma. The study was primarily designed to evaluate the clinical response, safety and tolerability of the combination of these therapies, and was carried out in the US, Israel and additional territories. The study is being conducted by BioLineRx under a collaboration agreement signed in 2016 between BioLineRx and MSD, through a subsidiary.

In July 2018, the Company announced the expansion of its immuno-oncology collaboration with MSD to include a triple combination arm investigating the safety, tolerability and efficacy of BL-8040, KEYTRUDA and chemotherapy as part of the Phase 2a COMBAT/KEYNOTE-202 study. The triple combination arm will focus on second-line pancreatic cancer patients.

BL-8040, BioLineRx’s lead oncology platform, is a CXCR4 antagonist that has been shown in several clinical trials to be a robust mobilizer of immune cells to peripheral blood and to be effective at inducing direct tumor cell death. In addition, clinical findings have demonstrated the ability of BL-8040 to mediate infiltration of T-cells into tumors that were previously immunologically "cold" and devoid of immune cell infiltrate. Immune checkpoint inhibitors (such as KEYTRUDA) produce anti-cancer effects by increasing the activity of T-cells through blockade of the interaction between the immune checkpoint receptor PD-1, on T-cells, and its ligand PD-L1, on tumor cells. Pancreatic cancers have very little T-cell infiltrate, making them less susceptive to checkpoint blockade than other tumors that are infiltrated by T-cells. Therefore, combining BL-8040 with immune checkpoint blockade is predicted to increase the responsiveness of pancreatic cancer patients to immunotherapy. Further increase in the sensitivity of pancreatic cancer cells to BL-8040 and KEYTRUDA may be achieved by chemotherapy-mediated immunogenic cell death and exposure of new tumor antigens, resulting in activation of new anti-cancer T cell clones.

About BL-8040

BL-8040 is a short synthetic peptide for the treatment of hematological malignancies, solid tumors, and stem cell mobilization. It functions as a high-affinity best-in-class 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 and immune-cells, sensitization of cancer cells to chemo- and bio-based anti-cancer therapies, and direct anti-cancer effect by inducing programmed cell death (apoptosis). BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

On December 11, 2018 OncoSec Medical Incorporated (OncoSec) (NASDAQ:ONCS), a company developing intratumoral cancer immunotherapies, reported the presentation of new data that suggests treatment with TAVO (tavokinogene telseplasmid) has the ability to improve immune responses in heavily pretreated, inoperable and locally advanced triple negative breast cancers by increasing tumor infiltrating lymphocyte (TIL) density, increasing effector cytokines, and upregulating immune-related gene expression, factors associated with long-term response to anti-PD1 antibodies (Press release, OncoSec Medical, DEC 11, 2018, View Source [SID1234532009]).

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The now completed Pilot TNBC study, OMS-140 (NCT02531425), was designed to determine whether a single cycle of TAVO monotherapy could enhance anti-tumor immune responses in a TNBC salvage setting. Specifically, a comparative analysis of patient’s pre-TAVO tumor and blood samples to the post-TAVO tumor and blood samples demonstrated that, with only a single cycle of TAVO, a treatment-related increase of CD8+ TIL was observed in four of 10 patients, while also demonstrating a relative decrease in immune suppressive cells.

Nanostring analysis (a novel platform for quantification of gene expression) of the tumor microenvironment revealed a meaningful increase of immune-related transcripts while on treatment. The investigator also evaluated the peripheral blood through a longitudinal analysis of PBMCs (peripheral blood mononuclear cells), and, in doing so, noted an increase of both effector and partially exhausted T cells, which complements the reduced frequency of immune-suppressive MDSC (myeloid-derived suppressor cells) reported earlier this year at AACR (Free AACR Whitepaper).

These data, along with increased effector cytokines noted in serum, demonstrate both local and systemic immune responses with only one cycle of TAVO in this difficult to treat patient population. Additionally, as observed in other clinical trials with TAVO, this study showed that TAVO is safe and well tolerated in this patient population.

These data, as well as other clinical and immunological data, were presented at the 2018 San Antonio Breast Cancer Symposium (SABCS) taking place December 4-8 in San Antonio, Texas.

"The immunological signatures described here, including conversion of non-immunogenic tumors into immunologically active lesions, are very encouraging, especially when considering that patients with very advanced disease received only one cycle of TAVO," said Dr. Christopher Twitty, Chief Scientific Officer of OncoSec. "Late-stage triple negative breast cancer patients have very few treatment options, and those that are available, come with serious toxicities and limited effectiveness. Recent data suggest that some patients with triple negative tumors will benefit from treatment with PD-1 checkpoint inhibitors, but only if the patient’s tumor is immunologically active," continued Dr. Twitty. "This study represents the potential of a safe and effective immunotherapy to turn non-immunogenic tumors into an immunologically active tissue, expanding the benefits of PD-1 checkpoint inhibitors to a much broader subset of women with triple negative breast cancer, which would be an important advance for the treatment of these patients."

As previously reported, a subset of patients that completed a single cycle of TAVO in this study, were sequentially treated with an anti-PD-1 checkpoint therapy (nivolumab). Importantly, some of these patients, one with prior disease progression on anti-PD-L1 antibody monotherapy, experienced robust clinical responses beyond the TAVO treated lesions. One of these patients continues to be treated with TAVO under a compassionate use protocol.

Based on these findings, OncoSec and Merck initiated a second TAVO Phase 2 study in TNBC, KEYNOTE-890, to evaluate the combination of TAVO with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in approximately 25 patients with treatment-refractory, inoperable or metastatic triple negative breast cancer (NCT03567720).

Since KEYNOTE-890 opened in October, investigators have already enrolled five patients into the trial. The KEYNOTE-890 study is testing the combination in patients with inoperable locally advanced or metastatic TNBC who have progressed on more than one line of prior therapy. Patients will be treated with the combination of TAVO with pembrolizumab. The primary endpoint is to assess efficacy as measured by objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

On December 10, 2018 Achilles Therapeutics ("Achilles" or "the Company"), a biopharmaceutical company using neoantigens to develop personalised cancer immunotherapies, reported that it has appointed Dr Edwin Moses as Chairman of its Board of Directors (Press release, Achilles Therapeutics, DEC 10, 2018, View Source [SID1234531978]). In addition, Dr Iraj Ali, currently Interim CEO, will become the permanent, full-time CEO of the Company.

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Dr Moses was most recently CEO of Ablynx NV which was acquired by Sanofi for $4.8Bn in 2018. Edwin was CEO at Ablynx for more than 12 years and built it from a small R&D-focused organisation into a five hundred person commercial-ready business with a broad biologics pipeline including a wholly-owned product for a rare hematologic indication which was approved for use in Europe earlier this year. At Ablynx, Edwin led the Euronext Brussels listing, multiple successful private and public financings and the NASDAQ listing in 2017. He was also responsible for delivering a series of multi-billion-pound collaborations with major pharmaceutical companies.

Edwin has more than 25 years of Board level experience, both as CEO and Chairman, in more than 10 European life science companies. During his career to date, Edwin has raised more than €500M in equity and debt financing.

Dr Ali joined Achilles in January 2018 as Interim CEO, whilst also serving as a Partner of Syncona Ltd, Achilles’ founding investor. He joined Syncona in 2012 and was an investment partner and Board member of Nightstar Therapeutics, Blue Earth Diagnostics and Achilles Therapeutics. Dr Ali was previously with McKinsey & Company where he was involved in several major pharmaceutical launches across developed and emerging markets and was a co-founder of McKinsey’s US launch practice and leader of speciality launches in Europe.

Edwin Moses, Chairman of Achilles, said:

"I am delighted to become the Chairman of Achilles. The Company was founded by world-leading experts in the understanding of cancer evolution, bioinformatics and the development of cell-based immunotherapies. The potential of the technology is extremely exciting and together with a dynamic and talented management team and Board, I am very much looking forward to building an international immunotherapeutic company and realizing the full potential of the core science to develop products to improve the lives of patients and create value for investors."

Iraj Ali, CEO of Achilles, added:

"We are on the brink of a revolution in cancer therapy driven by the convergence of bioinformatics and immuno-oncology, both of which are developing at a staggering pace. I have been involved with the development of the Achilles concept from its inception and I am delighted to become the CEO on a permanent basis and to welcome someone of Edwin’s calibre to be Chairman of our Board. Edwin brings exceptionally relevant experience to Achilles and together with his stewardship, I look forward to leading this business through its next phase of growth."

Dr Martin Murphy, Chief Executive Officer of Syncona Investment Management Ltd commented:

"Iraj has played an integral role in the development of Syncona and has played an instrumental part in the foundation and subsequent progress of Achilles. We are delighted that he has chosen to transition from being the interim CEO to take on the role on a full-time basis. It serves to underscore our shared belief in Achilles, which is a truly innovative healthcare business with an opportunity to grow into a globally competitive commercial company."

Achilles also recently announced the appointment of industry leader Michael F. Giordano, M.D., previously the Head of Immuno-Oncology and Oncology Development at Bristol-Myers Squibb responsible for approvals of Yervoy and Opdivo, as a non-executive director to its Board.

The Achilles Board composition is now as follows:

Edwin Moses, Chairman

Iraj Ali, Chief Executive Officer

Martin Murphy, Non-Executive Director

Elisa Petris, Observer

Professor Karl Peggs, Founder Director

Ian Walker, Non-Executive Director

Michael F. Giordano, Non-Executive Director

– Ends –

Further information:

Achilles Therapeutics

Dr Iraj Ali – Chief Executive Officer

+44 (0)1438 906 906

[email protected]

JW Communications

Julia Wilson

+44 (0)7818 430877

[email protected]

Consilium Strategic Communications

Mary-Jane Elliott, Sukaina Virji, Melissa Gardiner

Tel: +44 (0) 203 709 5000

Email: [email protected]