November 2, 2016 Medivir AB (Nasdaq Stockholm: MVIR) reported that it has entered into an agreement to acquire two clinical stage oncology programs from Tetralogic Pharmaceuticals Corporation (Nasdaq: TLOG), advancing and expanding its clinical pipeline (Press release, Medivir, NOV 2, 2016, View Source [SID1234528400]). The acquisition includes remetinostat, a skin-directed HDAC inhibitor, and birinapant, a bivalent SMAC mimetic, and all intellectual property and data associated with Tetralogic’s HDAC inhibitor and SMAC mimetic projects.

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Remetinostat Clinical Program
Remetinostat is a topical, skin-directed inhibitor of histone deacetylases (HDACs) and has a strong link to Medivir´s existing expertise in protease inhibition. The compound was designed to effectively inhibit HDACs within cutaneous lesions, but to be rapidly broken down in the bloodstream, preventing the side effects associated with systemically administered HDAC inhibitors.

Remetinostat is currently in a late phase II program aimed to treat early stage cutaneous T-cell lymphoma (CTCL), a chronic, orphan hematologic cancer that presents in the skin. There are few drugs available for the treatment of the disease, and those currently available have generally poor tolerability. As a result, patients are in need of safe and effective new treatment options which remetinostat may represent. The estimated addressable market for early-stage CTCL in the US alone is approximately USD 900m annually.

Medivir currently plans to start a phase III trial with remetinostat in the second half of 2017.

Birinapant Clinical Program
Birinapant is a bivalent, second mitochondrial activator of caspases (SMAC) mimetic that binds cellular inhibitor of apoptosis proteins (cIAPs) and induces their degradation. cIAPs are part of the ubiquitin proteasome system, and birinapant therefore ties in well to Medivir’s existing interests in modulators of protein ubiquitination. Medivir currently plans to start two different clinical studies with birinapant:

A phase I study in combination with KeytrudaTM(pembrolizumab), a PD-1 inhibitor from Merck & Co., Inc. (MSD outside of the US and Canada, "MSD"), in patients with solid tumours, subject to transfer to Medivir of the clinical trial agreement between Tetralogic and MSD and receipt of KeytrudaTMsupply. Preclinical studies have shown that SMAC mimetics such as birinapant are able to enhance the response of T-cells to tumour antigens, and the objective of the planned phase I study is to investigate the safety of the combination and the potential of birinapant to enhance response rates seen with KeytrudaTMalone. PD-1 inhibitors such as KeytrudaTMare immuno-oncology products that have substantially improved treatment outcomes for patients with solid tumours. Revenues of PD-1 inhibitors as reported by MSD and Bristol-Myers Squibb in the last twelve months have totalled approximately USD 3.2b. The PD-1 inhibitor market is expected to continue to grow from increasing use and expansion of the number of indications for which they are approved.
A phase II program, to investigate birinapant in combination with platinum-based chemotherapy for the treatment for high-grade serous carcinomas (HGSCs), including ovarian cancer, in collaboration with clinical investigators at UCLA. The UCLA team have identified that platinum-resistant cells in HGSCs are highly susceptible to birinapant-platinum co-therapy in approximately half of patients, and have developed a bioassay to enable patient selection. High-grade serous carcinomas are tumours that are believed to be derived from cells in the fallopian tube and can present as ovarian, endometrial, tubal or peritoneal cancer. The majority of ovarian cancer cases are high-grade serous carcinomas and these patients have a very poor survival rate. The ovarian cancer market size overall is estimated to be USD 840m, with those patients resistant to platinum treatments representing the group with highest unmet need.
Financial Consideration and Third-Party Arrangements
The acquisition has been structured to provide an upfront cash payment, but with the majority of financial consideration tied to successful clinical development, regulatory approvals and sales milestones. Medivir will also assume agreements or certain obligations with other third parties, including the MSD agreement regarding KeytrudaTM, subject to confirmation from MSD.

The acquisition includes the following potential payments to Tetralogic and other third party licensees:

Upfront cash consideration of USD 12m;
Remetinostat development milestones through regulatory filings of up to USD 20m;
Remetinostat regulatory approval milestones of up to USD 45m;
Remetinostat tiered royalties capped at an aggregate of 13%;
Additional remetinostat commercialization milestones of up to USD 31m, primarily based on substantial sales achievement levels;
Birinapant development milestones and research support of up to USD 20m;
Birinapant tiered royalties capped at an aggregate of 10%; and
Additional birinapant commercialization milestones of up to USD 110m, primarily based on substantial sales achievement levels.
Strategic Overview
"This is a transformative transaction for Medivir and an important part of our strategy to expand our pipeline with programs in later stage clinical phases, shifting the balance from research to clinical development. The acquisition enables Medivir to build critical mass in development and secures visible value generation, with expected near-term and continuous news flow from multiple studies. These assets are complementary to our oncology efforts in early phases. Both programs have an excellent fit with the Medivir scientific platforms and we are uniquely positioned to recognize the value of both of Tetralogic’s clinical assets." says Niklas Prager, CEO & President of Medivir.

Richard Bethell, CSO of Medivir continues, "We are excited to have acquired these two projects, both of which have the potential to meaningfully advance the care of cancer patients. Medivir has a track record of discovering and developing drugs that are targeted to specific tissues, so we are well placed to rapidly progress remetinostat for the treatment of early-stage CTCL. Many patients with this disease are urgently in need of new treatments that are both safe and effective. We also believe that birinapant, through its effects on both immune and tumour cells, offers the potential to improve the treatment of a number of different cancers. We look forward to rapidly advancing both of these agents into the next round of clinical studies."

Closing Conditions
The transaction is subject to confirmation by MSD of agreement transfer to Medivir, the consent of the Tetralogic Senior Noteholders, approval of the Tetralogic shareholders and other customary closing conditions. Medivir expects the transaction to close by year end 2016.

Aduro Biotech has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Aduro BioTech, NOV 2, 2016, View Source [SID1234516172]).

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On November 2, 2016 Bellicum Pharmaceuticals and Hospital Bambino Gesù , the European reference point for the care and in pediatric research, announced the beginning of an extended collaboration centered on the development of new therapies with genetically modified cells for treating onco-hematological diseases (Press release, OPBG, NOV 2, 2016, View Source [SID1234516577]).

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In detail, the arrangement concerns the preclinical and clinical development of products advanced cell therapy engineered with the suicide gene new CaspaCIDe of Bellicum, for the production of lymphocytes through modified chimeric and T-lymphocyte receptors artificial receptor (CAR T and TCR) specific for certain antigens , including CD19.

The two entities will jointly develop T cells modified with chimeric receptors (CAR T) and other cellular therapies developed by the Child Jesus and engineered with the safety switch CaspaCIDe of Bellicum, designed to reduce or eliminate the cells, when necessary, that is, presence of possible side effects related to the same cells.

Under the agreement, Bellicum will provide the necessary financial support in exchange for worldwide commercialization rights to certain developed cell therapies, while the Baby Jesus will keep the rights for the purpose of ricerc a. The Hospital of the Holy See will perform clinical research and studies for the application of advanced cell therapies in pediatric patients, initially through two clinical trials based on the use of genetically modified lymphocytes with specific chimeric receptors and CD19 antigens GD2 , respectively, in patients pediatric suffering from acute lymphoblastic leukemia, and neuroblastoma.

The trial will begin in the first half of 2017 . In addition, the Baby Jesus will produce, within its pharmaceutical plant, genetically modified cells necessary for European experiments , including T lymphocytes transduced with PRAME (Preferentially Expressed Protein in Melanoma) and employable in patients with acute myeloid leukemia or bone cancer.

On November 2, 2016 Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune diseases, asthma and allergic diseases and cancer, reported financial results for the third quarter ended September 30, 2016 and provided a review of pipeline and corporate highlights (Filing, Q3, Xencor, 2016, NOV 2, 2016, View Source [SID1234516344]).

"During the third quarter, we initiated clinical trials across our internal pipeline of XmAb programs, including Phase 1 studies of subcutaneously administered XmAb5871 and XmAb7195, and a first-in-human Phase 1 study of our lead immuno-oncology bispecific antibody candidate, XmAb14045," said Bassil Dahiyat, Ph.D., president and chief executive officer of Xencor. "With these milestones complete and a strong cash position, we expect to report data from multiple clinical trials in the year ahead, while also initiating studies of additional bispecific oncology candidates and continuing to explore the breadth of our Fc engineering technology."

Pipeline Highlights:

XmAb5871: XmAb5871 is a first-in-class monoclonal antibody that targets CD19 with its variable domain and that uses Xencor’s XmAb immune inhibitor Fc domain to target FcγRIIb, a receptor that inhibits B-cell function. In March 2016, Xencor initiated Phase 2 clinical studies of XmAb5871 for the treatment of IgG4-Related Disease (IgG4-RD) and systemic lupus erythematosus (SLE), and in July 2016, Xencor initiated a Phase 1 trial of subcutaneously administered XmAb5871.

· Preliminary data from IgG4-RD Phase 2 trial to be presented at the American College of Rheumatology (ACR) 2016 Annual Meeting on November 13, 2016 in Washington, DC; additional data expected in 2017
· Initial data from subcutaneous administration trial expected in 2017
· Initial data from SLE Phase 2 trial expected in 2018

XmAb7195: XmAb7195 is a first-in-class monoclonal antibody that targets IgE with its variable domain and uses Xencor’s XmAb Immune Inhibitor Fc domain to target FcγRIIb, resulting in three distinct mechanisms of action for reducing IgE levels. In September 2016, Xencor initiated a Phase 1b multi-dose trial of subcutaneously administered XmAb7195 for the treatment of allergic disease.

· Initial data from subcutaneous administration Phase 1b trial expected in 1H17

Bispecific Oncology Pipeline: Xencor’s initial bispecific antibody programs are tumor-targeted antibodies that contain both a tumor antigen binding domain and a cytotoxic T-cell binding domain. These bispecific antibodies activate T cells for highly potent and targeted killing of malignant cells. Their XmAb Fc domains confer long circulating half-lives, stability and ease of manufacture. In September 2016, Xencor initiated a Phase 1 trial of XmAb14045 in acute myeloid leukemia (AML) and other CD123-expressing hematologic malignancies.

· Initial data from XmAb14045 Phase 1 trial expected in 2017
· Initiation of Phase 1 trial for XmAb13676 in B-cell malignancies expected in 1Q17; initial data expected in 2018

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· Investigational New Drug (IND) application filing for XmAb18087 in neuroendocrine tumors expected in 2017
· IND application filing for XmAb20717, a PD-1 x CTLA-4 dual checkpoint inhibitor, in multiple oncology indications expected in 2018

Partnered XmAb Programs: Nine pharmaceutical companies and the National Institutes of Health (NIH) are advancing novel drug candidates either discovered at Xencor or that rely on Xencor’s proprietary XmAb technology. Seven such programs are currently undergoing clinical testing.

· In September, MorphoSys announced that it began dosing in the safety evaluation portion of a Phase 2/3 combination trial of XmAb5574/MOR208 with bendamustine in patients with relapsed or refractory diffuse large B-cell lymphoma (B-MIND trial). Following the Phase 2 safety evaluation, the study is expected to transition into a pivotal Phase 3 part in 2017.

Third Quarter Ended September 30, 2016 Financial Results

Cash, cash equivalents and marketable securities totaled $301.9 million as of September 30, 2016, compared to $193.3 million on December 31, 2015. The increase reflects the $150 million upfront payment received from Novartis in July 2016, net of spending for the nine months ended September 30, 2016.

Revenues for the third quarter ended September 30, 2016 were $7.8 million compared to $3.5 million for the same period of 2015. Revenues for the nine months ended September 30, 2016 were $81.1 million, compared to $6.0 million for the same period in 2015. Revenues in the three and nine-month period ended September 30, 2016 were earned primarily from the Company’s Novartis and Amgen collaborations, compared to revenues for the same period in 2015, which were earned primarily from the Company’s Novo Nordisk, Alexion and CSL collaborations.

Research and development expenditures for the third quarter ended September 30, 2016 were $14.1 million, compared to $10.6 million for the same period in 2015. Total research and development expenses for the nine-month period ended September 30, 2016 were $38.5 million, compared to $23.3 million for the same period in 2015. The increased spending on research and development for the three and nine months ended September 30, 2016 is primarily due to additional spending on Xencor’s XmAb5871 clinical programs and bispecific technologies, including its initial bispecific oncology clinical candidates, XmAb14045 and XmAb13676.

General and administrative expenses in the third quarter ended September 30, 2016 were $3.0 million compared to $3.2 million for the same period in 2015. Total general and administrative expenses for the first nine months of 2016 were $10.0 million, compared to $8.5 million in the first nine months of 2015. Decreased spending on the general and administration areas for the three months ended September 30, 2016 over the same period in 2015 is due to lower stock-based compensation charges in the quarter, while the increased spending for the nine months ended September 30, 2016 over the same period in 2015 reflects additional legal and accounting fees for compliance related activities and additional stock-based compensation charges.

Non-cash, share-based compensation expense for the first nine months of 2016 was $5.9 million compared to $3.4 million for the first nine months of 2015.

Net loss for the third quarter ended September 30, 2016 was $8.1 million, or $(0.20) on a fully diluted per share basis, compared to a net loss of $10.0 million, or $(0.25) on a fully diluted per share basis, for the same period in 2015. For the nine months ended September 30, 2016, net income was $32.7 million or $0.78 on a fully diluted per share basis, compared to net loss of $25.3 million, or $(0.66) on a fully diluted per share basis, for the same period in 2015. The lower loss for the three months ended September 30, 2016 over the loss reported for the same period in 2015 is primarily due to revenue earned from the Company’s Amgen collaboration, while the income earned for the nine months ended September 30, 2016 over the same period in 2015 is primarily due to revenue earned from the Company’s Novartis collaboration.

The total shares outstanding was 41,138,851 as of September 30, 2016, compared to 40,477,003 shares outstanding as of September 30, 2015.

Financial Guidance

Based on current operating plans, Xencor expects to have cash to fund research and development programs and operations beyond the end of 2019.

On November 2, 2016 PTC Therapeutics, Inc. (NASDAQ: PTCT) reported a corporate update and reported financial results for the third quarter ending September 30, 2016 (Press release, PTC Therapeutics, NOV 2, 2016, View Source [SID1234516313]).

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"For the past 18 years, we have focused significant effort towards developing Translarna for those affected by Duchenne," stated Stuart W. Peltz, Ph.D. Chief Executive Officer, PTC Therapeutics, Inc. "Over 400 Duchenne patients have participated in our clinical trials dating back to 2005 and the vast majority continue to remain on Translarna including approximately 130 boys in the United States. With this high compliance rate, we believe these actions speak to the benefit Translarna is providing to patients in the U.S. and around the world. In the E.U., regulatory discussions continue and we anticipate an opinion from the CHMP before the end of the year. With respect to the U.S., we will continue to escalate our appeal so that we may have the opportunity to have the Translarna NDA submission reviewed by the FDA. Our goal remains to deliver this novel therapy to nonsense mutation Duchenne patients globally."

Key Third Quarter and Other Corporate Highlights:

Translarna net sales of $22M in the third quarter represents 125% year-over-year growth. Commercial access to Translarna continued to expand during the quarter with a significant number of new patients coming from England. While pricing and reimbursement discussions with a number of European countries are ongoing, PTC has now successfully concluded pricing and reimbursement negotiations in both Italy and Romania. PTC anticipates growth from both additional penetration into existing markets as well as expanding access in new geographies across Central and Eastern Europe, the Middle East and Latin America.
EMA regulatory discussions regarding Translarna’s marketing authorization are ongoing. PTC continues to interact with the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) in connection with the company’s ongoing request for annual renewal of its marketing authorization for Translarna. Following the company’s CHMP meeting in October, the committee requested additional information regarding the risk-benefit profile of Translarna, its efficacy and the design of a potential trial that would provide comprehensive clinical data. While we have provided information in response to the CHMP’s requests and expect to continue to engage in further interactions, recent dialogue has introduced a higher degree of uncertainty as to the outcome. PTC anticipates that an opinion regarding its marketing authorization renewal request will be adopted by the CHMP before the end of 2016. The current marketing authorization remains valid while the EMA assessment is ongoing and until a decision is made by the European Commission.
Appeal process of FDA’s Refuse to File regarding Translarna for DMD continues. As PTC previously stated, the RTF appeal could be an iterative process requiring multiple rounds before a conclusion. Having had its appeal denied, the company intends to continue the appeal to higher levels of the FDA. PTC continues to believe that the FDA can only accomplish a proper assessment of the data and analyses based on the results of the company’s extensive clinical research and experience in more than 400 boys in the context of a full and fair review. This would include an advisory committee meeting that allows DMD clinical experts and representatives of the patient community to express their views on Translarna for the treatment of nmDMD. PTC intends to provide an update following a final conclusion of the appeal process or, alternatively, following a determination by the company to pursue an alternate regulatory strategy for advancing the potential approval of Translarna for the treatment of nmDMD in the U.S.
ACT CF Phase 3 clinical trial results expected late first quarter 2017. PTC’s confirmatory Phase 3 ACT CF clinical trial, a 48-week placebo-controlled trial designed to evaluate the efficacy of Translarna in patients six years of age or older with nonsense mutation cystic fibrosis, is ongoing. Following feedback from the FDA and the company’s CHMP rapporteurs during the third quarter, PTC modified the protocol for ACT CF. In-line with clinical trials for other approved CF therapies, the primary endpoint of lung function as measured by FEV1 was updated from relative change to absolute change in percent predicted FEV1. Pulmonary exacerbations will be an important secondary endpoint.
SMA program advancing with Phase 2 SUNFISH trial initiated in Type 2/3 patients. PTC’s joint development program in Spinal Muscular Atrophy (SMA) with Roche and the SMA Foundation initiated a Phase 2 study in pediatric and adult Type 2/3 SMA patients. SUNFISH, is a two-part study investigating the safety, tolerability and efficacy of RG7916, an oral small molecule survival motor neuron 2 (SMN2) splicing modifier. The first part of the study will evaluate safety and tolerability through escalating doses of RG7916. After dose selection, the study will transition into the pivotal second part evaluating the efficacy of RG7916. Initiation of the pivotal second part of the study is expected to begin in 2017 and will trigger a $20 million milestone payment to PTC from Roche. A similarly designed two-part study to evaluate RG7916 in Type 1 SMA patients is expected to begin in the coming months.
PTC596 cancer stem cell program to advance in clinical development in 2017.
Phase 1 safety data from PTC’s clinical oncology program were recently presented at the European Society for Medical Oncology Congress. The ongoing Phase 1 dose-escalation study is evaluating the safety, tolerability and pharmacokinetics of PTC596 in patients with advanced solid tumors as a monotherapy. Preliminary results demonstrate that PTC596 is generally well tolerated at doses associated with exposures that achieved or exceeded efficacious target plasma concentrations in preclinical studies. Escalating doses are being evaluated for safety, pharmacodynamics, and to determine a target dose for subsequent studies. PTC596 is a novel, oral investigational drug that reduces the levels of BMI1, a protein that is required for cancer stem cell survival. Based on its proposed mechanism of action, PTC596 is expected to be most efficacious when used as part of combination therapy. Continued clinical development of PTC596 is being planned for 2017.
Third Quarter Financial Highlights:

Translarna net product sales were $22.0 million for the third quarter of 2016, representing a 125% increase versus $9.8 million in the third quarter of 2015. Net sales increased in conjunction with continued expansion of commercial access to Translarna for nonsense mutation DMD boys outside of the U.S.
Total revenues for the third quarter of 2016 were $23.0 million, an increase of $13.2 million or 135% compared to $9.8 million in the same period of 2015. The change in total revenue was primarily a result of the expanded commercial launch of Translarna.
GAAP R&D expenses were relatively flat at $31.4 million for the third quarter of 2016 compared to $30.6 million for the same period in 2015. Non-GAAP R&D expenses were $27.1 million for the third quarter of 2016, excluding $4.3 million in non-cash, stock-based compensation expense, compared to $26.8 million for the same period in 2015, excluding $3.8 million in non-cash, stock-based compensation expense.
GAAP SG&A expenses were $23.7 million for the third quarter of 2016 compared to $21.4 million for the same period in 2015. Non-GAAP SG&A expenses were $19.0 million for the third quarter of 2016, excluding $4.6 million in non-cash, stock-based compensation expense, compared to $17.1 million for the same period in 2015, excluding $4.2 million in non-cash, stock-based compensation expense. The increase in SG&A expense for the third quarter 2016 as compared to the prior year period primarily resulted from additional costs associated with commercial activities in support of Translarna across Europe and other regions.
Net interest expense for the third quarter of 2016 was $2.1 million compared to net interest expense of $0.9 million in the same period in 2015. The increase in interest expense is primarily a result of the $150 million convertible debt offering completed during mid-third quarter 2015. The debt was recorded on PTC’s balance sheet at a discount, which will be amortized over the life of the bond.
Net loss for the third quarter of 2016 was $35.2 million, a decrease of $8.1 million compared to a net loss of $43.2 million for the same period in 2015.
Cash, cash equivalents, and marketable securities totaled approximately $248.3 million at September 30, 2016 compared to approximately $338.9 million at December 31, 2015.
Shares issued and outstanding as of September 30, 2016 were 34.3 million, which includes 0.2 million shares of unvested restricted stock.
2016 Guidance:

PTC expects to achieve total ex-US nmDMD Translarna net sales in the middle of our guidance of $65 to $85 million for 2016.
Operating expenses for the full year 2016 are now anticipated to be between $180 million and $190 million, excluding expected non-cash stock-based compensation expense of approximately $35 million, for total operating expenses of approximately $215 million to $225 million. These expenses are in support of our ongoing clinical trials for Translarna in nmDMD and nmCF, commercial launch activities for Translarna outside of the U.S., and the continued research and clinical development of other product pipeline candidates.
PTC expects to end 2016 with cash and cash equivalents of approximately $220 million.