On April 19, 2021 Adaptate Biotherapeutics (Adaptate), a company focussed on developing antibody-based therapeutics for modulation of gamma delta T cells, reported that its existing investors, Abingworth and Takeda Pharmaceutical Company Limited (Takeda) have together made a further equity investment of $18 million (circa. £13 million) (Press release, Adaptate Biotherapeutic, APR 19, 2021, View Source;utm_medium=rss&utm_campaign=adaptate-biotherapeutics-raises-18-million-in-series-a2-funding [SID1234578168]). This funding brings the total raised since Adaptate’s inception in late 2019 to $34 million (circa. £25 million).

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The investment results from the rapid progress made by the Company over the past 18 months. The funds will be used to accelerate the progression of Adaptate’s lead therapeutic antibody programme towards the clinic and to expand its internal product pipeline. The Company’s growing portfolio includes both monoclonal and bispecific antibodies which target gamma delta T cells, a unique class of lymphocytes that bridge innate and adaptive immunity. The Company’s most advanced programmes are focussed on treatments for cancer patients with solid tumours. Adaptate’s antibodies selectively target gamma delta T cells, thereby offering the opportunity for superior efficacy and safety compared to conventional immunomodulatory therapies such as pan T cell activators.

The financing will also support the Company’s expansion, including further recruitment and increased laboratory and office space. This expansion exemplifies Adaptate’s rapid growth plans and the additional capacity will play a key role in further boosting research and development activities.

Dr Natalie Mount, CEO of Adaptate Biotherapeutics, said: "The funding is a great vote of confidence from our existing investors and testimony to the hard work and rapid progress we have made in the novel field of gamma delta T cell targeting antibodies. We are excited to continue this growth path and to progress our unique therapeutic antibodies towards clinical trials where we look forward to them making an impact on the treatments available to cancer patients."

Tim Haines, Chairman & Managing Partner, Abingworth, commented: "We have been impressed with the potential of Adaptate’s therapeutic antibody technology and the significant progress to date.. We are delighted to invest further, to enable the team to accelerate its very promising portfolio towards the clinic."

Loic Vincent, Head, Oncology Drug Discovery Unit, Takeda, added: "Takeda’s ongoing investment in Adaptate aligns closely with our pursuit of potentially life-changing treatments for cancer patients through novel immuno-oncology approaches. We look forward to continuing to work together on the potential of gamma delta T cell targeted therapies to achieve this goal."

On April 19, 2021 Sanofi reported that the European Commission (EC) approved Sarclisa (isatuximab) in combination with carfilzomib and dexamethasone (Kd) for the treatment of adult patients with relapsed multiple myeloma who have received at least one prior therapy (Press release, Sanofi, APR 19, 2021, View Source [SID1234578164]). This marks the second EC approval of Sarclisa in combination with a standard of care regimen in less than 12 months.

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"As there is no cure for multiple myeloma and patients often experience disease relapse, we must persist in our pursuit for additional treatment options. Nearly 30% of patients treated with the Sarclisa regimen had a profound response with undetectable levels of multiple myeloma," said Philippe Moreau, M.D., Department of Hematology, University Hospital of Nantes, France. "This new therapeutic regimen has the potential to become a standard of care for patients with relapsed multiple myeloma, who now have another treatment option earlier in the progression of their disease."

This EC approval closely follows the U.S. Food and Drug Administration (FDA) approval of Sarclisa for a similar indication in March 2021. In June 2020, Sanofi announced Sarclisa received EC approval in combination with another standard of care regimen, pomalidomide and dexamethasone (pom-dex), for the treatment of adult patients with relapsed and refractory MM who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on the last therapy.

"The EC approval of Sarclisa in combination with carfilzomib and dexamethasone means patients living with multiple myeloma in Europe can now receive Sarclisa in combination with two standard of care treatment regimens," said Peter C. Adamson, Global Development Head, Oncology and Pediatric Innovation at Sanofi. "The carfilzomib and dexamethasone combination represents an important standard of care in Europe. The Phase 3 IKEMA trial’s finding that the addition of Sarclisa to this regimen reduced the risk of progression or death by nearly half formed the basis for this important EC approval."

Sarclisa Efficacy and Safety Profile in Difficult-to-Treat Patients

This approval is based on data from the Phase 3 IKEMA study, a randomized, multi-center, open label clinical trial that enrolled 302 patients with relapsed MM across 69 centers spanning 16 countries. The primary endpoint of IKEMA was progression free survival (PFS). While median PFS, defined as time to disease progression or death, for Kd was 19.15 months, the median PFS for patients receiving Sarclisa added to carfilzomib and dexamethasone (Sarclisa combination therapy; n=179) had not been reached at the time of the pre-planned interim analysis. Sarclisa combination therapy reduced the risk of disease progression or death by 47% (hazard ratio 0.531, 99% CI 0.318-0.889, p=0.0007) versus standard of care Kd alone in patients with MM.

Secondary endpoints of the IKEMA trial assessed the depth of response for Sarclisa combination therapy compared to Kd, including overall response rate (ORR), complete response (CR), very good partial response (VGPR) and minimal residual disease (MRD)-negative response. The ORR remained similar for each arm at 86.6% for the Sarclisa combination therapy versus 82.9% for Kd but was not statistically significant. The rate of CR was 39.7% in the Sarclisa combination therapy arm and 27.6% in the Kd arm. The rate of VGPR or better was 72.6% for patients receiving Sarclisa combination therapy and 56.1% for patients receiving Kd. MRD-negativity was observed in 29.6% of patients in the Sarclisa combination therapy arm versus 13% of patients in the Kd arm, indicating that nearly 30% of patients treated with Sarclisa combination therapy achieved undetectable levels of MM at 10-5 sensitivity as measured by next generation sequencing (NGS). At the time of the interim analysis, overall survival (OS) data were still immature.

The most frequent adverse reactions (≥20%) were infusion reactions (45.8%), hypertension (36.7%), diarrhea (36.2%), upper respiratory tract infection (36.2%), pneumonia (28.8%), fatigue (28.2%), dyspnea (27.7%), insomnia (23.7%), bronchitis (22.6%), and back pain (22.0%). Serious adverse reactions occurred in 59.3% of patients receiving Sarclisa combination therapy and in 57.4% of patients receiving Kd. The most frequent serious adverse reaction was pneumonia (21.5%). Permanent discontinuation of treatment because of adverse reactions was reported in 8.5% of patients treated with Sarclisa combination therapy and in 13.9% of patients treated with Kd. Fatal adverse events were reported in 3.4% of patients treated with Sarclisa combination therapy and in 1.6% of patients treated with Kd.

Multiple Myeloma: An incurable cancer, despite available treatments

MM is the second most common hematologic malignancy1, with more than 130,000 new diagnoses of MM worldwide yearly.2 In Europe, approximately 39,000 patients are diagnosed with MM each year.3 Despite available treatments, MM remains an incurable malignancy, and is associated with significant patient burden. Since MM does not have a cure, most patients will relapse. Relapsed MM is the term for when the cancer returns after treatment or a period of remission. Refractory MM refers to when the cancer does not respond or no longer responds to therapy.

About Sarclisa

Sarclisa is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on MM cells. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a potential target for antibody-based therapeutics such as Sarclisa.

Sarclisa is approved in the EU, U.S., Switzerland, UK, Canada, Australia, Japan, Russia, the UAE, South Korea, Taiwan and Qatar in combination with pom-dex for the treatment of certain adults with relapsed refractory MM. It is also approved in the U.S. in combination with carfilzomib and dexamethasone for the treatment of adult patients with relapsed or refractory MM who have received one to three prior lines of therapy. In the U.S., the generic name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the FDA.

Sarclisa continues to be evaluated in multiple ongoing Phase 3 clinical trials in combination with current standard treatments across the MM treatment continuum. It is also under investigation for the treatment of other hematologic malignancies and solid tumors. The safety and efficacy of these additional uses have not been reviewed by any regulatory authority worldwide.

On April 19, 2021 Kazia Therapeutics Limited (ASX: KZA;NASDAQ: KZIA), an oncology-focused drug development company, reported that it has entered into a worldwide exclusive licensing agreement and a master services agreement with Evotec SE (FRA: EVT), a leading European drug discovery and development company, for EVT801, a small-molecule, first-in-class oncology drug candidate. Kazia expects to launch a phase I clinical trial of EVT801 in CY2021 (Press release, Kazia Therapeutics, APR 19, 2021, View Source [SID1234578160]).

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Key Points

Evotec has granted Kazia an exclusive global worldwide license to develop, manufacture, and commercialise EVT801 in all territories and indications.
Under the terms of the agreement, Kazia will pay an immediate upfront of €1 million (AU$ 1.6 million), contingent milestones of up to €308 million (AU$ 480 million) related to achievement of clinical, regulatory, and commercial outcomes over the lifetime of the drug, and a tiered single-digit royalty on net sales.
Evotec is a leading drug discovery and development company, headquartered in Hamburg, Germany, and listed on the Frankfurt Stock Exchange.
EVT801 is a small-molecule inhibitor of VEGFR3. Its primary activity is to inhibit lymphangiogenesis, the formation of new lymphatic vessels around a growing tumour. By doing so, EVT801 is expected to starve the tumour of vital nutrients and to reduce metastasis. EVT801 also has marked activity on the immune system within the tumour and may therefore enhance the activity of immuno-oncology therapies.
Kazia and Evotec have also entered into a master services agreement, under which the two companies will collaborate closely on the further development of EVT801.
EVT801 was originally discovered by Sanofi (NASDAQ: SNY), the largest pharmaceutical company in France and among the five largest in the world and was developed through a partnership between Sanofi and Evotec.
Kazia expects to launch a phase I clinical trial in CY2021. The initial exploratory indications for EVT801 include renal cell carcinoma (kidney cancer), hepatocellular carcinoma (liver cancer), and soft tissue sarcoma.
Kazia CEO, Dr James Garner, commented, "We are delighted to add this tremendously exciting new compound to the Kazia pipeline. Evotec have done first-class work in the early development of EVT801, and the preclinical data package is exceptionally strong. We intend to fast track a phase I clinical trial of the drug, which we expect to commence in CY2021."

He added, "As we have built Kazia over the past five years, our strategy has been to assemble a portfolio of world-class development candidates through in-licensing. The EVT801 transaction is wholly consistent with that strategy. We have demonstrated, through the paxalisib program, our ability to add value to a development candidate, and we intend to similarly accelerate EVT801 via a rich and innovative development program."

Evotec CEO, Dr Werner Lanthaler, commented, "we are very pleased to partner with Kazia for this promising asset, for which we have high hopes. Our corporate strategy does not provide for Evotec to take EVT801 through clinical trials itself, so we have sought to identify a partner who can do justice to the drug’s potential. We recognise Kazia’s track record and look forward to working together to make EVT801 available to patients and clinicians."

EVT801

EVT801 is a small molecule inhibitor of vascular endothelial growth factor receptor 3 (VEGFR3). It is orally available, and so can be administered to patients by mouth.

For more than two decades, one of the most successful approaches in the treatment of cancer has been to target angiogenesis, the formation of new blood vessels. Drugs which inhibit angiogenesis, such as Avastin (bevacizumab), starve the growing tumour of nutrients. However, inhibiting angiogenesis also results in hypoxia (low levels of oxygen) around the tumour, and this is thought to generate resistance to treatment. Almost all cancers treated with current anti-angiogenic drugs will eventually develop resistance.

An alternative approach, which may avoid this problem, is to target lymphangiogenesis, which is the formation of new lymphatic vessels. Doing so achieves many of the same objectives as targeting angiogenesis but may avoid the problem of resistance induced by hypoxia. Moreover, the lymphatic system is a common route by which tumours spread (metastasise) throughout the body, and so inhibiting lymphangiogenesis may help to limit the ability of the tumour to spread.

In recent years, several new drug candidates have attempted to inhibit lymphangiogenesis. For example, Nexavar (sorafenib) inhibits several forms of VEGFR, as well as other targets, and is approved for the treatment of renal cell carcinoma and hepatocellular carcinoma. Several drugs described as angiokinase inhibitors are in development, and some of these inhibit VEGFR3. However, each of these drugs has multiple targets, leading in many cases to significant side effects. The distinguishing feature of EVT801 is a high degree of specificity for VEGFR3, which should allow it to minimise toxicity.

In addition, EVT801 has shown powerful evidence in the laboratory of an ability to change the balance of immune cells within the tumour. Many tumours are resistant to the newest generation of immuno-oncology therapies because they do not contain the right immune cells for the drugs to act upon. It is hoped that administration of EVT801 may help to sensitise these tumours to immuno-oncology therapies such as Keytruda (pembrolizumab) and Opdivo (nivolumab) and thereby extend their use.

Kazia expects to explore all these potential uses of EVT801 during the clinical program. The initial focus will be on a phase I study, which is expected to be conducted at one or more leading hospitals in France and to commence in CY2021.

Master Services Agreement

In parallel with the license agreement, Kazia and Evotec have entered into a Master Services Agreement (MSA), under which they will collaborate on the further development of EVT801. Kazia intends to utilise Evotec’s substantial capabilities and expertise in research, clinical trial management, biomarker development, and manufacturing, to expedite the development of EVT801.

Investor Conference Call

Kazia is pleased to invite investors to attend a conference call to further discuss the EVT801 in-licensing.

The call will be held on Tuesday 20 April 2021 at 8:00am, Sydney time (AET), which is 6pm on Monday 19 April in New York (ET) and 3pm on Monday 19 April in San Francisco (PT).

Participants will need to pre-register for the call via the following link:

Registration Link: View Source

Click the ‘Register Now’ button and follow the prompts to complete pre-registration. You will then receive a calendar invite with dial in numbers, a passcode and a PIN to dial into the conference call.

On April 19, 2021 Genmab A/S (Nasdaq: GMAB) reported the initiation of a share buy-back program to mitigate dilution from warrant exercises and to honor our commitments under our Restricted Stock Units program (Press release, Genmab, APR 19, 2021, View Source [SID1234578159]).

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The share buy-back program is expected to be completed no later than June 30, 2021 and comprises up to 200,000 shares.

The following transactions were executed under the program from April 12, 2021 to April 16, 2021:

Details of each transaction are included as an appendix to this announcement.

Following these transactions, Genmab holds 217,977 shares as treasury shares, corresponding to 0.33% of the total share capital and voting rights.

The share buy-back program is undertaken in accordance with Regulation (EU) No. 596/2014 (‘MAR’) and the Commission Delegated Regulation (EU) 2016/1052, also referred to as the "Safe Harbour Regulation." Further details on the terms of the share buy-back program can be found in our company announcement no. 11 dated February 23, 2021.

On April 19, 2021 ERYTECH Pharma (Nasdaq & Euronext: ERYP), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported the completion of enrollment of the first treatment cohort and the escalation to the next and potentially final dose level in a Phase 1 investigator sponsored clinical trial (IST), named rESPECT, of its lead product candidate eryaspase for the first-line treatment of pancreatic cancer (Press release, ERYtech Pharma, APR 19, 2021, https://erytech.com/erytech-announces-completion-of-first-cohort-in-a-phase-1-investigator-sponsored-trial-of-eryaspase-in-first-line-pancreatic-cancer/ [SID1234578158]).

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