On March 26, 2019 NANOBIOTIX (Euronext: NANO – ISIN: FR0011341205 – the ‘‘Company’’), a clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported that the Company has clarity on its regulatory pathway in the treatment of Head and Neck cancers for first-in-class radioenhancer NBTXR3 (Press release, Nanobiotix, MAR 26, 2019, View Source [SID1234534630]).
The announcement follows pre-IND feedback from the US FDA received on March 18, 2019.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Stage III and IV Head and Neck cancers include large primary tumors which may invade underlying structures and/or spread to regional nodes. Treatment of these locally advanced forms of the disease—which makes up more than 50% of all Head and Neck cancers—requires aggressive, concerted measures that often remain a clinical challenge with an estimated 5-year survival rate of 50% with the current standard of care.

Within the Stage III and IV Head and Neck cancers patient population, the Company targets a subpopulation of patients, who have a higher risk of recurrence, or a poorer prognosis as they have an inability to receive cisplatin, the frontline chemotherapy drug for advanced Head and Neck cancers. Additionally, the localization of the tumor focuses on oropharynx, hypopharynx, and oral cavity – representing the majority of Head and Neck cancers.

Based on US FDA feedback, the Company plans to design an Overall Survival (OS)-based, randomized, event-driven Phase II/III clinical trial. 50% of patients will receive standard of care radiotherapy combined with NBTXR3 while the other 50% will receive radiotherapy in combination with cetuximab. The expected total number of patients to participate in this global clinical trial is approximately 600, and an efficacy interim analysis is planned.

Notably, the US FDA has not objected to the use of the data from the dose-escalation phase of the Company’s European Phase I clinical trial in elderly and frail patients with locally advanced Head and Neck cancers as well as the Company’s current CMC (chemical, manufacturing and control) development plan.

The Company plans to initiate its global clinical trial authorization process with US FDA in 2H2019.-Ends

About NBTXR3

NBTXR3 is a first-in-class product candidate designed to destroy tumors and metastasis when activated by radiotherapy. NBTXR3 has a high degree of biocompatibility and requires one single administration before the whole radiotherapy treatment. Nanobiotix believes NBTXR3 has the ability to fit into current worldwide standards of radiation care. Nanobiotix’s broad clinical program includes 7 clinical trials. In June 2018, Nanobiotix established human proof of concept for this first-in-class product candidate in its Soft Tissue Sarcoma (STS) Phase III clinical trial. 2 NBTXR3 is actively being studied in head and neck cancer with locally advanced squamous cell carcinoma of the oral cavity or oropharynx in elderly and frail patients who are unable to receive chemotherapy or cetuximab and have very limited therapeutic options. Promising results from these clinical studies have been observed from the ongoing Phase I/II trial regarding the local control of tumors. Nanobiotix is also running an Immuno-Oncology development program. In the United States, Nanobiotix has received approval from the US FDA to launch a clinical study of NBTXR3 activated by radiotherapy in combination with anti-PD1 antibodies in lung, and head and neck cancer patients (head and neck squamous cell carcinoma and non-small cell lung cancer). The other ongoing NBTXR3 trials are treating patients with liver cancers (hepatocellular carcinoma and liver metastasis), locally advanced or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with concurrent chemotherapy, and prostate adenocarcinoma. The first market authorization process (CE Marking) is ongoing in Europe in the STS indication.

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

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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

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

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

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

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

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

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

DOWNLOADS
Press release
PDF, 281.7 KB
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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.