On June 22, 2017 Repare Therapeutics Inc. reported a US$68 million Series A financing to advance its platform and pipeline of novel medicines that target genetically defined weaknesses of cancers. Founding investor Versant Ventures co-led the round with MPM Capital (Press release, Repare Therapeutics, JUN 22, 2017, View Source [SID1234520721]). They were also joined by other syndicate investors including Fonds de solidarité FTQ, Celgene Switzerland LLC, an affiliate of Celgene Corporation, and BDC Capital’s Healthcare Venture Fund.

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With this financing, Repare emerges from Versant’s Discovery Engines after an 18-month stealth period during which the company advanced its leading CRISPR-enabled synthetic lethality drug discovery platform, identified several promising oncology targets and moved multiple programs into preclinical development. Founders Daniel Durocher, Ph.D., Agnel Sfeir, Ph.D., and Frank Sicheri, Ph.D., and their respective institutions, played instrumental roles in the company’s formation and growth in partnership with Versant.

"Versant’s commitment to and confidence in Repare’s distinct science has enabled the company to build the team, operations and initial programs away from the spotlight," said Repare CEO Lloyd M. Segal. "With the added leadership of MPM and this syndicate, we are financed to achieve our goal of testing our multiple new, precision oncology therapeutics in a clinical setting."

The core concept of synthetic lethality is that while a tumor can tolerate individual defects in its DNA, there exist combinations of defects that lead to the malignancy’s destruction. The recent approvals of several PARP inhibitors provide clear proof-of-principle for the approach of inducing synthetic lethality. Repare and its founders have developed large-scale and novel methods for discovering additional drug targets that, when inhibited, may induce synthetic lethality. New drugs directed at these targets hold promise to improve cancer treatment both as single therapies and in combination with existing drugs and treatments.

In addition to Segal, a Versant Entrepreneur-in-Residence, Repare’s seasoned management team also includes R&D Head Michael Zinda, Ph.D., who built and led AstraZeneca plc’s Oncology iMed Bioscience group in Boston; and VP of Discovery Cameron Black, Ph.D., an accomplished 18-year leader of Merck Frosst’s medicinal chemistry efforts. Repare has a 20-member team based in Montreal and Boston. To further guide this important investment both Jerel Davis, Ph.D., managing director at Versant, and Todd Foley, managing director at MPM Capital, will join Repare’s board of directors.

"The fields of synthetic lethality and DNA repair have a rich, 20-year history and are poised to deliver impactful new cancer treatments," said Davis. "We are impressed by the speed and precision with which Repare, in collaboration with its founders and scientific advisors, generated impressive insights and multiple novel targets."

Repare’s first disclosed program targets DNA-directed DNA polymerase theta (PolQ), a central component of a pathway that repairs double-strand breaks in cancer cells. NYU School of Medicine has licensed to Repare exclusive rights to drug discovery work targeting PolQ, developed by Dr. Sfeir with the support of NYU Office of Therapeutics Alliances (OTA). This unique polymerase is highly expressed in ovarian, breast and a number of other cancers. In parallel, Repare is progressing several additional programs, with an aim to put its first compound in the clinic in 2019.

"We evaluated nearly every opportunity in the synthetic lethality space and have complete conviction that Repare, its founders and its SAB members represent the leaders in the field," said Foley. "MPM is dedicated to investing in and building companies that seek to find cures for cancer and save lives and we look forward to the advancement of Repare’s programs and the development of these meaningful medicines."

Repare’s founders and scientific advisors are leaders in synthetic lethality and tumor repair machinery research. In addition to Dr. Sfeir from the Department of Cell Biology and the Skirball Institute of Biomolecular Medicine at NYU Langone Medical Center and Drs. Durocher and Sicheri from Toronto’s Lunenfeld-Tanenbaum Research Institute, Repare has assembled a world-class scientific advisory board, including:

Samuel Aparicio, Ph.D., chair of the Breast Cancer Program at BC Cancer Agency and professor of pathology and laboratory medicine at UBC, Vancouver.
Jim Carmichael, M.D. FRCP, lead of the Protein Homeostasis Thematic Center of Excellence at Celgene Corporation. He previously was U.K. regional director of medical science at AstraZeneca plc following its acquisition of KuDOS, where he was CMO and responsible for clinical development of olaparib.
Ronny Drapkin, M.D., Ph.D., director of the Penn Ovarian Cancer Research Center and director of gynecologic cancer research at the Basser Center for BRCA at the University of Pennsylvania.
Laurie Glimcher, M.D., president and CEO of the Dana-Farber Cancer Institute, Richard and Susan Smith Professor of Medicine at Harvard Medical School.
Mark Pegram, M.D., director of the breast cancer oncology program at Stanford Women’s Cancer Center and co-director of Stanford’s molecular therapeutics program.
Richard Wood, Ph.D. FRS, Grady F. Saunders Distinguished Professor in Molecular Biology at the University of Texas MD Anderson Cancer Center.

About Repare

Repare is developing new, precision oncology drugs for patients that target specific vulnerabilities of tumor cells. Its approach integrates insights from several fields of cell biology including DNA repair and synthetic lethality. Repare’s platform combines a proprietary, high-throughput, CRISPR-enabled gene editing target discovery method with high-resolution protein crystallography, computational biology and clinical informatics. The company is backed by leading global healthcare investors including founding investor Versant Ventures and MPM Capital. For additional information, please visit www.reparerx.com.

About Versant

Versant Ventures is a leading healthcare investment firm committed to helping exceptional entrepreneurs build the next generation of great healthcare companies. The firm invests across the healthcare sector and at all stages of company development, with an emphasis on the discovery and development of novel therapeutics. With $2.3 billion under management and offices in North America and Europe, Versant has built a team with deep investment, operating, and scientific expertise that enables a hands-on approach to company building. Since the firm’s founding in 1999, more than 65 Versant companies have achieved successful acquisitions or IPOs. For more information, please visit www.versantventures.com.

About MPM Capital

MPM Capital is an early‐stage life sciences venture firm founding and investing in companies that seek to cure major diseases by translating scientific innovations into positive clinical outcomes. MPM’s portfolio of companies aims to revolutionize the face of medicine across multiple areas including cancer, neuroscience, metabolic disorders, and regenerative medicine. With its experienced and dedicated team of operating executives and medical and scientific advisory board, MPM is powering novel medical breakthroughs that transform patients’ lives. MPM has more than $2.6 billion dollars in assets under management and is currently investing from two funds ─ the BV2014 and UBS Oncology Impact Fund. For further information, please visit www.mpmcapital.com.

About the Fonds de solidarité FTQ

The Fonds de solidarité FTQ is a development capital fund that channels the savings of Quebecers into investments. As at November 30, 2016, the organization had $12.2 billion in net assets, and through its current portfolio of investments has helped create and protect over 187,000 jobs. The Fonds is a partner in more than 2,600 companies and has nearly 618,000 shareholder-savers. fondsftq.com.

About BDC Capital

With more than $2 billion under management, BDC Capital is the investment arm of BDC, serving as a strategic partner to Canada’s most innovative and high potential firms. It offers a range of equity, venture capital and flexible growth and transition capital solutions to help Canadian entrepreneurs scale their businesses into global champions. To find out more, visit bdc.ca/capital.

On June 23, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the US Food and Drug Administration (FDA) approved Rituxan Hycela (rituximab and hyaluronidase human) for subcutaneous (under the skin) injection, for the treatment of adults with the following blood cancers: previously untreated and relapsed or refractory follicular lymphoma, previously untreated diffuse large B-cell lymphoma (DLBCL), and previously untreated and previously treated chronic lymphocytic leukaemia (CLL) (Press release, Hoffmann-La Roche, JUN 22, 2017, View Source [SID1234519664]). This new treatment includes the same monoclonal antibody as intravenous Rituxan (rituximab) in combination with hyaluronidase human, an enzyme that helps to deliver rituximab under the skin.

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"With today’s approval of Rituxan Hycela, people with three of the most common blood cancers now have a new treatment option which provides efficacy comparable with intravenous Rituxan and can be delivered under the skin in minutes instead of hours through IV infusion," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "People who benefit from Rituxan may receive years of repeated treatments for their blood cancer, so an option that reduces the administration time can be important."

The FDA approval is based on results from clinical studies, which demonstrated that subcutaneous administration of
Rituxan Hycela resulted in non-inferior levels of rituximab in the blood (pharmacokinetics) and comparable clinical efficacy outcomes compared to intravenous Rituxan. One of the studies showed the majority (77%) of patients preferred Rituxan Hycela over intravenous Rituxan, with the most common reason being that administration required less time in the clinic. People can only receive Rituxan Hycela after at least one full dose of intravenous Rituxan.

With the exception of local skin (cutaneous) reactions, the incidence and profile of adverse reactions for Rituxan Hycela were comparable with those for intravenous Rituxan. The most common (≥20%) adverse reactions observed with Rituxan Hycela in people with follicular lymphoma were infections, low white blood cell count (neutropenia), nausea, constipation, cough and fatigue. The most common adverse reactions in people with DLBCL were infections, neutropenia, hair loss (alopecia), nausea and low red blood cell count (anemia). The most common adverse reactions in people with CLL were infections, neutropenia, nausea, low platelet count (thrombocytopenia), fever (pyrexia), vomiting and reddening of the skin (erythema) at the injection site.

Rituxan Hycela will be available to people in the United States within one to two weeks, and intravenous Rituxan will continue to be available.

About the Rituxan Hycela Clinical Development Program
The approval of Rituxan Hycela is based on results from clinical studies that together represented nearly 2,000 people. The studies were the following:
SABRINA (NCT01200758): Phase III combination with chemotherapy and maintenance study in previously untreated follicular lymphoma

SAWYER (NCT01292603): Phase Ib study in previously untreated chronic lymphocytic leukaemia (CLL)
MabEase (NCT01649856): Phase III study in previously untreated diffuse large B-cell lymphoma (DLBCL)
PrefMab (NCT01724021): Phase III patient preference study in previously untreated follicular lymphoma and DLBCL

About MabThera/Rituxan (rituximab)
MabThera/Rituxan is a therapeutic monoclonal antibody that binds to a particular protein – the CD20 antigen – on the surface of normal and malignant B-cells. It then recruits the body’s natural defenses to attack and kill the marked B-cells. Stem cells (B-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B-cells to regenerate after treatment and return to normal levels within several months.

Rituxan first received FDA approval for the treatment of relapsed indolent non-Hodgkin Lymphoma (NHL) in 1997 and was the first targeted cancer medicine approved by the U.S. Food and Drug Administration (FDA). MabThera was approved in the EU in June 1998, and has since been used to treat more than 2.7 million people with specific blood cancers. For more than 15 years, the efficacy and safety of MabThera/Rituxan has been documented in more than 300 phase II/III clinical studies. MabThera/Rituxan has been approved for the treatment of several blood cancers, specifically, certain types of NHL and for chronic lymphocytic leukaemia (CLL). It continues to be studied in other types of blood cancers and disease areas where CD20-positive cells are believed to play a role.

MabThera is known as Rituxan in the United States, Japan and Canada. Genentech, a member of the Roche Group, and Biogen collaborate on Rituxan in the United States, and Roche markets MabThera in the rest of the world, except Japan, where MabThera is co-marketed by Chugai and Zenyaku Kogyo Co. Ltd.

About Rituxan Hycela
Rituxan Hycela is a co-formulation of the same monoclonal antibody as intravenous MabThera/Rituxan and Halozyme Therapeutics’ proprietary hyaluronidase human, an FDA-approved enzyme that facilitates the delivery of a large volume of medicine under the skin. Rituxan Hycela can be administered in five to seven minutes, compared to 1.5 to four hours for intravenous MabThera/Rituxan. It is known as the subcutaneous (SC) formulation of MabThera (rituximab) in the European Union.

About Follicular Lymphoma
Follicular lymphoma is the most common indolent (slow-growing) form of non-Hodgkin lymphoma (NHL), accounting for about one in five cases of NHL1. It is considered incurable and relapse is common. Every day, more than 50 people in Europe are diagnosed this type of NHL2. It is estimated that each year, more than 75,000 people are diagnosed with follicular lymphoma worldwide2.

About Diffuse Large B-Cell Lymphoma (DLBCL)
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL3. DLBCL is an aggressive (fast-growing) type of NHL, which is generally responsive to treatment in the frontline4. However, as many as 40% of patients will relapse, at which time salvage therapy options are limited and survival is short4. Approximately 123,000 people worldwide are estimated to be diagnosed with DLBCL each year5.

About Chronic Lymphocytic Leukaemia (CLL)
Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in the Western world6. CLL mainly affects men and the median age at diagnosis is about 70 years7. Worldwide, the incidence of all leukaemias is estimated to be over 350,0006 and CLL is estimated to affect around one-third of all people newly diagnosed with leukaemia8.

On June 22, 2017 Idera Pharmaceuticals, Inc. (NASDAQ:IDRA), a clinical-stage biopharmaceutical company developing toll-like receptor and RNA therapeutics for patients with cancer and rare diseases, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for IMO-2125, an agonist of endosomal Toll-like receptor (TLR) 9 for the treatment of melanoma Stages IIb to IV (Press release, Idera Pharmaceuticals, JUN 22, 2017, View Source;p=irol-newsArticle&ID=2282632 [SID1234519650]).

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Idera is currently conducting the Phase 2 portion of the ipilimumab combination arm of a Phase 1/2 clinical trial of intratumoral IMO-2125 in patients with anti-PD-1 refractory metastatic melanoma. The objectives of the current trial are to evaluate IMO-2125’s safety, tolerability and clinical activity. The company expects to complete enrollment of the Phase 2 multicenter trial in the second half of 2017 with overall response rate (ORR) data available in the first quarter of 2018. The company has submitted an abstract to provide an update of clinical data from the ongoing trial at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress being held in September, in Spain.

"The Orphan Drug Designation bestowed by the FDA today, represents another important step in the development of IMO-2125," stated Joanna Horobin, M.B. Ch.B., Idera’s Chief Medical Officer. "A substantial proportion of patients with metastatic melanoma do not benefit from anti-PD-1 therapy. For these patients, with PD-1 refractory melanoma, ipilimumab offers a modest benefit with an overall response rate of 10-13%1,2. Our goal is to significantly improve on this through the combination of IMO-2125 with ipilimumab. We are increasingly encouraged with the data seen to date and look forward to providing our next clinical data update."

Idera is also enrolling a second arm in the Phase 1/2 clinical trial in patients with PD-1 refractory melanoma to study the combination of IMO-2125 and pembrolizumab which is currently in the dose escalation phase.

In addition to the above mentioned clinical trial, the company recently initiated a trial of IMO-2125 monotherapy in refractory solid tumors, including PD-1 refractory melanoma.

Orphan Drug Designation is granted by the FDA Office of Orphan Products Development to drugs intended for the treatment of a rare disease or condition that affects fewer than 200,000 people in the United States. This designation provides certain incentives, including eligibility for federal grants, research and development tax credits, waiver of PDUFA filing fees and a seven-year marketing exclusivity period, once the product is approved and as long as orphan drug designation is maintained.

The approval of an orphan drug designation request does not alter the standard regulatory requirements and processes for obtaining marketing approval of an investigational drug. Sponsors must establish safety and efficacy of a compound in the treatment of a disease through adequate and well-controlled studies.

About the Phase 1/2 trial of IMO-2125 in PD-1 Refractory Melanoma
The Phase 1/2 trial of intratumoral IMO-2125 in combination with ipilimumab or pembrolizumab is being conducted in patients who are refractory to anti-PD-1 therapy. The phase 1 portion of the trial was conducted at MD Anderson Cancer Center and the phase 2 portion of the trial is being conducted at multiple clinical sites. In the Phase 1 arms of the trial, four dose levels of IMO-2125 (4, 8, 16 and 32 mg) have been administered intratumorally in one selected lesion at weeks 1, 2, 3, 5, 8 and 11, in combination with the standard dosing regimens of ipilimumab or pembrolizumab, beginning on week 2. The Phase 2 expansion portion of the trial utilizes a Simon two-stage design. If at least 2 of the first 10 patients treated at the Phase 2 dose experience confirmed response the futility hurdle has been met and the trial may continue to enroll. Phase 2 will evaluate 21 patients at the phase 2 dose. Tumor biopsies have been collected pre- and post-24 hours of the first dose of IMO-2125, as well as at 8 and 13 weeks to evaluate multiple immune markers. Clinical activity has been evaluated by the RECIST v1.1 criteria. Clinical data from this study has been presented at SITC (Free SITC Whitepaper) 2017, ASCO (Free ASCO Whitepaper)-SITC 2017 and AACR (Free AACR Whitepaper) 2017, and can be found also on Idera’s corporate website at View Source

About IMO-2125
Toll-like receptors (TLRs) play a central role in the innate immune system, the body’s first line of defense against invading pathogens, as well as damaged or dysfunctional cells including cancer cells. The innate immune system is also involved in activating the adaptive immune system, which marshals highly specific immune responses to target pathogens or tissue. Cancer cells may exploit regulatory checkpoint pathways to avoid being recognized by the immune system, thereby shielding the tumor from immune attack. Checkpoint inhibitors such as agents targeting CTLA4 or programmed cell death protein 1 (PD1) are designed to enable the immune system to recognize tumor cells. In this setting, intratumoral TLR9 agonist administration may increase the tumor-infiltrating lymphocytes (TILs), and thereby potentiate anti-cancer activity of checkpoint inhibitors in the injected tumor as well as systemically.

IMO-2125, Idera’s TLR9 agonist, has been created using the company’s proprietary chemistry-based discovery platform. IMO-2125 has been shown in various scientific presentations and publications to activate dendritic cells and induce interferon. Idera selected IMO-2125 to advance into clinical development in combination with checkpoint inhibitors based on this immunological profile. In previously completed clinical trials, subcutaneous administration of IMO-2125 was very well tolerated in about 114 patients with hepatitis C. Idera has conducted further preclinical and clinical research evaluating the potential of IMO-2125 to enhance the anti-tumor activity of other checkpoint inhibitors in cancer immunotherapy with data has been presented at several scientific and medical conferences during the past few years. The posters from these presentations can be found at View Source

About Metastatic Melanoma
Melanoma is a type of skin cancer that begins in a type of skin cell called melanocytes. As is the case in many forms of cancer, melanoma becomes more difficult to treat once the disease has spread beyond the skin to other parts of the body such as by through the lymphatic system (metastatic disease). Melanoma accounts for only one percent of skin cancer cases, but causes a large majority of skin cancer deaths. The American Cancer Society estimates that in 2017, there will be 87,110 new cases of melanoma in the U.S., and about 9,730 will die of this disease. Based on proprietary Idera research, the company anticipates by the year 2025, there will be roughly 13,000 anti-PD-1 refractory metastatic melanoma patients.