Mirati Therapeutics to Collaborate with Sanofi on Phase 1/2 Study Evaluating Combination of adagrasib with a SHP2 Inhibitor in KRAS G12C-mutated Lung Cancer

On October 7, 2021 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported a non-exclusive clinical collaboration agreement with Sanofi to evaluate the combination of adagrasib, the Company’s investigational KRASG12C inhibitor, with Sanofi’s investigational SHP2 inhibitor SAR442720, also known as RMC-4630 (Press release, Mirati, OCT 7, 2021, View Source [SID1234590960]). The Phase 1/2 dose escalation and expansion study will evaluate the combination in patients with previously-treated non-small cell lung cancer (NSCLC) and KRASG12C mutations.

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"Mirati is aggressively advancing a broad adagrasib development program, which includes pursuing novel combination approaches including through this collaboration with Sanofi," said Charles M. Baum, M.D., Ph.D., president, founder and head of research and development, Mirati Therapeutics, Inc. "There is strong scientific rationale for combining a SHP2 inhibitor with adagrasib, which may help optimize clinical outcomes for patients with KRASG12C-dependent tumors."

SHP2 is upstream of KRAS and mediates cellular signaling through the RAS/MAP kinase pathway and is frequently overactive in various types of cancer. KRASG12C inhibition and SHP2 inhibition have complementary mechanisms of action and have demonstrated additive anti-tumor activity in pre-clinical models.

Under the terms of the agreement, Sanofi will be responsible for sponsoring and operating the Phase 1/2 study, and jointly with Mirati, will oversee and share costs of the study.

About Adagrasib (MRTX849)

Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C mutated cancers, as the KRASG12C protein regenerates every 24−48 hours. Adagrasib is a being evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including non-small cell lung cancer (NSCLC), colorectal cancer and pancreatic cancer. For more information visit Mirati.com/science.

About SAR442720 (RMC-4630)

SAR442720 (RMC-4630) is a potent and orally bioavailable small molecule that is designed to selectively inhibit the activity of SHP2, an upstream cellular protein that plays a central role in modulating cell survival and growth by transmitting signals from receptor tyrosine kinases to RAS. SAR442720 (RMC-4630) is the focus of an exclusive global development and commercialization agreement between Sanofi and Revolution Medicines.

NorthStar Medical Radioisotopes Announces Launch of New Website to Showcase Company’s Expanding Commercial Success, Pipeline Progress and Plans for the Future

On October 7, 2021 NorthStar Medical Radioisotopes, LLC, a global innovator in the development, production and commercialization of radiopharmaceuticals used for therapeutic applications and medical imaging, reported the launch of its newly redesigned corporate website (Press release, NorthStar Medical Radiostopes, OCT 7, 2021, View Source [SID1234590982]). The new site includes increased functionality and a number of enhancements. Expanded content includes latest product information, updates on NorthStar’s significant campus expansion, its growing partnerships and dynamic pipeline in therapeutic and SPECT radiopharmaceuticals, and the latest in career opportunities as the Company continues to grow and expand. NorthStar welcomes visitors to its new site at: www.northstarnm.com.

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"We are very pleased to launch the new NorthStar corporate website that reflects our excitement and enthusiasm in working to provide global solutions for reliable medical radioisotope supply for patient health," said Stephen Merrick, President and Chief Executive Officer of NorthStar Medical Radioisotopes. "We redesigned the website to provide details on NorthStar’s progress and expansion, our talented and experienced management team and employee base, our robust plans for the future and our commitment to patient health. This is an exciting time for NorthStar that warrants amplified communication and updates to our audiences. We believe there is no better way to share this information than with a highly relevant website that consistently provides streamlined, timely content."

2021 Q3 Report: Global Trends in Biopharma Transactions

On October 7, 2021 Locust Walk reported that deal team members compile key statistics and trends on strategic transactions and financings (Press release, Locust Walk Partners, OCT 7, 2021, View Source;utm_medium=rss&utm_campaign=2021-q3-report-global-trends-in-biopharma-transactions [SID1234591035]). Our 2021 Q3 Report: Global Trends in Biopharma Transactions applies the latest data to analyze current activities in the life sciences deal landscape. ​

In this report you can find an overview and analysis of the following across the biopharma market in the US, Europe, and Asia (Japan and China):​

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Key performance indicators for the life science market​​
IPO and private financing activity and performance​​
Deal activity for strategic partnership and M&A​
A look ahead and our predictions of the future

United States

Biotech indices declined in Q3 2021 (-1.2% NBI, -4.0% BTK), compared to the 0.2% gains of the benchmark S&P 500 this quarter​
The US biopharma IPO momentum slowed in Q3 in terms of total aggregate deal value but with slightly higher deal volume compared to Q2​
The healthcare SPAC IPO market which began to cool down in Q2 2021 continued its cooling in Q3, with the volume and aggregate deal value of biotech dedicated SPACs falling to near pre-pandemic levels​
Despite the apparent slowdown from the previous quarter, public and private financing activity remains strong relative to historical standards​
Biopharma companies from the IPO Classes of 2019, 2020, and 2021, on average, all underperformed the major biotech indices this quarter​
Strong deal flow among licensing deals demonstrated sustained interest in strategic licensing transactions. Additionally, a dramatic increase in M&A average deal size revealed that the market values clinical-stage biotechnology companies

Europe

The steadily impressive increases in private investment into EU biotech since Q1 2020 has taken a break, raising just over $1B in Q3 2021, a fall of ~35% after the record-setting of ~$1.6B raised in Q2 2021 but still higher than Q3 in 2020 or 2019
Public financings slowed down significantly in Q3 compared to the last two quarters. There were only five small IPOs, all in home exchanges; no biopharmas have crossed the pond this quarter to go public on the US markets
European M&A activity stays consistent in terms of deal volume but total deal value back towards levels seen in Q1 2020
Notably, Q3 EU biopharma licensing agreements surpassed $8.1B in aggregate value, beating the impressive $7.8B of Q2. The deal activity in this quarter was again driven by a strong focus on immuno-oncology, but also by the revival of CNS through three significant deals

Japan

The biotech sector in Q3 2021 fell -13.8% with noticeable drops end of July while the pharma sector stayed flat, and overall growth of the two sectors since the beginning of 2020 is underperforming market​
All 5 in-licensing deals in Q3 2021 involved over $200M in deal size, and are split between either phase 3 assets or discovery stage transactions​
Following a strong quarter in venture financing in Q2 2021, the trend continues in Q3 which featured 9 deals with aggregate value of $50M; volume and value in 9 months of 2021 already beat the full year record in 2020​

China

Average share price of top Chinese pharma dropped by 14.1% due to speculations that the tightening of regulation for IT companies may also happen in the health care sector, while the SSE Composite Index was stable​
In-licensing deal volume and value in Q3 2021 outperform Q2 the previous year: 21 in-licensing deals closed including 16 deals with over $50M in total deal size and 15 with over $5M upfront payment​
Out-licensing activity was slow in Q3, but with large deal size: RemeGen’s $2.6B deal for ADC program to Seagen​
Venture financing for biotech companies continue to exceed previous levels, as 35 companies raised capital for an aggregate total of $2.4B in Q3 alone

Alligator carries out a 100 percent secured rights issue of approximately SEK 257 million

On October 7, 2021 The Board of Directors of Alligator Bioscience AB (publ) ("Alligator" or "the Company") reported that , subject to approval by the Extraordinary General Meeting on 8 November 2021, resolved to carry out a rights issue of shares with preferential rights for the Company’s existing shareholders of approximately SEK 257 million (the "Rights Issue") (Press release, Alligator Bioscience, OCT 7, 2021, View Source [SID1234590892]). The Company has received subscription commitments from a selection of the Company’s larger existing shareholders, including the AP4, Roxette Photo NV and Omentum S.A., amounting to approximately SEK 43 million, corresponding to approximately 17 percent of the Rights Issue. Furthermore, the Company has entered into agreements on guarantee commitments of approximately SEK 214 million, which secures the Rights Issue up to 100 percent. In addition, Öhman Fonder and all members of the Company’s board and management with shareholdings in the Company have expressed their intention to subscribe for their respective pro rata share in the Rights Issue. Alligator will use the proceeds from the Rights Issue to conduct phase II studies for mitazalimab, preparations for and initiation of phase II studies for ATOR-1017 and further development of other pipeline candidates. The Rights Issue is subject to approval by the Extraordinary General Meeting on 8 November 2021, and the notice of the Extraordinary General Meeting will be announced in a separate press release.
Summary

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One (1) existing share in the Company entitles to three (3) subscription rights. Two (2) subscription rights entitle to subscription of one (1) new share, i.e., a subscription ratio of 3:2.
The subscription price is SEK 2 per new share, which, assuming the Rights Issue is fully subscribed, results in the Company receiving issue proceeds of approximately SEK 257 million before deduction of transaction costs.
The record date for the Rights Issue is 10 November 2021 and the subscription period runs from and including 12 November 2021 up to and including 26 November 2021.
The last day of trading in the Alligator share including the right to participate in the Rights Issue is 8 November 2021.
The board’s resolution on the Rights Issue is subject to approval by the Extraordinary General Meeting on 8 November 2021. Major shareholders, who together represent approximately 17 percent of the shares and votes in the Company, have undertaken to vote for the Rights Issue at the Extraordinary General Meeting.
Major shareholders have expressed their support for the Rights Issue through subscription commitments amounting to approximately SEK 43 million, corresponding to approximately 17 percent of the Rights Issue. Furthermore, the Company has entered into agreements on guarantee commitments of approximately SEK 214 million, corresponding to approximately 83 percent of the Rights Issue, which secures the Rights Issue up to 100 percent. The guarantee commitments consist partly of a so-called top guarantee and partly of a bottom guarantee. In addition, Öhman Fonder and all members of the Company’s board and management have expressed their intention to subscribe for their respective pro rata share in the Rights Issue.
The Company intends to publish a prospectus regarding the Rights Issue on 9 November 2021.

Background and reason for the Rights Issue

Alligator is active in the phases of drug development that range from idea and early research to clinical phase II studies in patients. This includes, among other things, the development and optimization of new drug candidates, evaluation of preclinical efficacy and safety, and finally confirmatory clinical studies on cancer patients.

Alligator has shown strong Proof of Mechanism data in Phase I studies for mitazalimab, Alligator’s most advanced immuno-oncology candidate. In 2021, the Company’s focus has been on preparations for the inclusion of the first patient in the clinical phase II study OPTIMIZE-1. The first patient was successfully included in September 2021 and interim efficacy data are estimated for the end of the fourth quarter of 2022. In order to balance the risk in the Company’s development portfolio and to increase the likelihood of clinical success, Alligator is planning a second phase II study with mitazalimab, OPTIMIZE-2. In the study, mitazalimab is planned to be combined with current standard of care in renal cell carcinoma, bladder cancer or hepatocellular carcinoma. OPTIMIZE-2 is expected to start in the second half of 2022.

In June 2021, new promising data from the Phase I study with ATOR-1017 were presented, confirming the therapeutic potential and demonstrating clear signals of proof of mechanism in combination with a favorable safety profile. Previous interim data, presented in the fall of 2020, from the ongoing Phase I study in patients with advanced cancer showed a promising safety profile for ATOR-1017, with only a few drug-related side effects all being mild or moderate (grade 1 or 2). Preparations are ongoing to start clinical Phase II studies, which is expected to take place during the third quarter of 2022.

To ensure continued successful development in accordance with the Company’s business plan and strategy, Alligator has resolved to carry out the Rights Issue. The Rights Issue is estimated to provide Alligator with approximately SEK 257 million before transaction costs. The board assesses that the working capital requirement for the coming twelve-month period is met by available cash and the net proceeds from the Rights Issue.

The expected net proceeds from the Rights Issue will, in the following order of priority and with an approximate proportion indicated in parentheses, be used for:

Conduction of phase II studies with mitazalimab (65 percent)
Preparations for and initiation of phase II study for ATOR-1017 (15 percent)
Development of other pipeline candidates (20 percent)

Terms of the Rights Issue

Those who are registered as shareholders on the record date, 10 November 2021, have the preferential right to subscribe for new shares in the Rights Issue in relation to the number of shares held on the record date. One (1) existing share in the Company entitles to three (3) subscription rights. Two (2) subscription rights entitle to subscription of one (1) new share, i.e., a subscription ratio of 3:2. In addition, investors are offered the possibility to subscribe for shares without subscription rights.

If not all newly issued shares are subscribed for by exercise of subscription rights, allotment of the remaining shares shall be made within the highest amount of the Rights Issue: firstly, to those who have subscribed for shares by exercise of subscription rights (regardless of whether they were shareholders on the record date or not) and who have applied for subscription of shares without exercise of subscription rights and if allotment to these cannot be made in full, allotment shall be made pro rata in relation to the number of subscription rights that each and every one of those, who have applied for subscription of shares without exercise of subscription rights, have exercised for subscription of shares; secondly, to those who have applied for subscription of shares without exercise of subscription rights and if allotment to these cannot be made in full, allotment shall be made pro rata in relation to the number of shares the subscriber in total has applied for subscription of shares; and thirdly, to those who have provided underwriting commitments with regard to subscription of shares, in proportion to such underwriting commitments. To the extent that allotment in any section above cannot be done pro rata, allotment shall be determined by drawing of lots.

The subscription price is SEK 2 per new share. Provided that the Rights Issue is fully subscribed, the share capital will increase by a maximum of SEK 51,399,802.80 by a new issue of a maximum of 128,499,507 new shares. In the event of full subscription, the Rights Issue will provide Alligator with approximately SEK 257 million before deduction of issue costs. Shareholders who choose not to participate in the Rights Issue will, provided that the Rights Issue is fully subscribed, have their ownership diluted by approximately 60 percent, but are able to financially compensate for this dilution by selling their subscription rights.

Subscription of shares shall take place during the period from and including 12 November 2021 to and including 26 November 2021. The board has the right to extend the subscription and payment period. A possible extension of the subscription period shall be announced by press release no later than the last subscription day in the Rights Issue, i.e. 26 November 2021. Trading in subscription rights takes place on Nasdaq Stockholm during the period from and including 12 November 2021 to and including 23 November 2021 and trading in paid subscribed shares (Sw. Betalda tecknade aktier) during the period from and including 12 November 2021 until the Rights Issue has been registered with the Swedish Companies Registration Office (Sw. Bolagsverket).

Subscription commitments, guarantee commitments and declarations of intent

Alligator has received subscription commitments from a selection of the Company’s larger existing shareholders, including the AP4, Roxette Photo NV and Omentum S.A., amounting to approximately SEK 43 million, corresponding to approximately 17 percent of the Rights Issue. Furthermore, the Company has entered into agreements on guarantee commitments in the form of a so-called bottom guarantee of approximately SEK 188 million, corresponding to approximately 73 percent of the Rights Issue, and a so-called top guarantee of approximately SEK 26 million, corresponding to approximately 10 percent of the Rights Issue. In addition, Öhman Fonder and all members of the Company’s board and management with shareholdings in the Company, including Søren Bregenholt (CEO), Anders Ekblom (Chairman of the board), Marie Svensson (CFO), Peter Ellmark (CSO), Veronica Wallin (board member) and Hans-Peter Ostler (board member), have expressed their intentions to subscribe for their respective pro rata share in the Rights Issue. The bottom guarantee ensures, provided that subscription corresponds to at least the subscription commitments, that approximately 90 percent of the Rights Issue is subscribed and paid for. Through the top guarantee, provided that subscription corresponds to at least the subscription commitments and the bottom guarantee, that 100 percent of the Rights Issue is subscribed and paid for.

For the guarantee commitments, compensation is paid either in cash or in the form of newly issued shares in the Company. The subscription price for any shares issued to guarantors shall correspond to 90 percent of the volume-weighted average share price (VWAP) for the Company’s share on Nasdaq Stockholm during the subscription period in the Rights Issue (i.e. during the period 12 – 26 November 2021), however no lower than the subscription price in the Rights Issue. In order to enable new issues of shares as guarantee compensation to the guarantors who choose to receive guarantee compensation in newly issued shares, the board has proposed that the Extraordinary General Meeting on 8 November 2021, which is proposed to resolve on the approval of the Rights Issue, also resolves on authorization for the board to resolve on new issues of such shares to guarantors.[1]

Preliminary timeline for the Rights Issue

8 November 2021

Extraordinary General Meeting

8 November 2021

Last day of trading incl. preferential rights

9 November 2021

First day of trading excl. preferential rights

9 November 2021

Estimated publication of prospectus

10 November 2021

Record date

12 November – 23 November 2021

Trading in subscription rights

12 November – 26 November 2021

Subscription period

12 November 2021 – Until the Rights Issue is registered at the Swedish Companies Registration Office

Trading in paid subscription shares (Sw. "BTA")

1 December 2021

Estimated publication of outcome in the Rights Issue

Lock-up agreements

In connection with the Rights Issue, the Company has undertaken towards the Joint Global Coordinators, subject to customary exceptions, not to issue additional shares or other share-related instruments for a period of 180 days after the end of the subscription period in the event of an issue with preferential rights for existing shareholders, and 90 days after the end of the subscription period in the event of an issue without preferential rights for existing shareholders. In addition, the Company’s board members and senior executives who own shares in Alligator, subject to customary exceptions, have undertaken, towards the Joint Global Coordinators, not to transfer or otherwise sell their shares for a period of 180 days after the end of the subscription period.

Extraordinary General Meeting

The board’s resolution on the Rights Issue is subject to approval by the Extraordinary General Meeting on 8 November 2021. Notice of the Extraordinary General Meeting will be announced in a separate press release.

Prospectus

Full terms and conditions for the Rights Issue, as well as other information about the Company and information about subscription commitments, guarantee commitments and lock-up commitments will be presented in the prospectus that the Company is expected to publish around 9 November 2021 (the "Prospectus").

Advisers

DNB Markets, a part of DNB Bank ASA, Sweden Branch and Redeye AB act as Joint Global Coordinators in connection with the Rights Issue. Setterwalls Advokatbyrå AB acts as legal adviser to Alligator and Baker & McKenzie Advokatbyrå KB acts as legal adviser to the Joint Global Coordinators in connection with the Rights Issue. Aktieinvest FK AB acts as the issuing agent in the Rights Issue.

Curis Announces New Preclinical Data Highlighting the Potential of CA-4948 in Multiple Hematologic Malignancies Presented at the AACR-NCI-EORTC Virtual Conference on Molecular Targets and Cancer Therapeutics

On October 7, 2021 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported two poster presentations with new preclinical data for CA-4948, a first-in-class small molecule IRAK4 inhibitor, at the AACR (Free AACR Whitepaper)-NCI-EORTC Virtual Conference on Molecular Targets and Cancer Therapeutics (Press release, Curis, OCT 7, 2021, View Source [SID1234590924]).

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"In ongoing Phase 1 clinical trials, CA-4948 has already demonstrated anti-tumor activity in non-Hodgkin’s lymphoma, acute myeloid leukemia and myelodysplastic syndromes. New preclinical data presented at AACR (Free AACR Whitepaper)-NCI-EORTC today support the potential of CA-4948 in additional hematologic cancers," said James Dentzer, President and Chief Executive Officer of Curis.

"Notably, these new preclinical data indicate that CA-4948 is synergistic with small molecules targeting BCR signaling, including both idelalisib and ibrutinib, and suggest it may help overcome or reduce secondary resistance to these therapies in marginal zone lymphoma. In addition, these data demonstrate that CA-4948 can cross the blood brain barrier and improve survival, in a dose-dependent manner, providing additional preclinical support for the study of CA-4948 in patients with primary central nervous system (pCNS) lymphoma, one of the most aggressive forms of lymphoma and a clear area of unmet need for patients." Mr. Dentzer added.

Details of the presentations are as follows:

Title: Pharmacological inhibition of IRAK-4 with CA-4948 is beneficial in marginal zone lymphoma models with secondary resistance to PI3K and BTK inhibitors
Author: Francesca Guidetti, Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland
Poster Number: P073

Title: The IRAK4 inhibitor CA-4948 demonstrates antitumor activity in a preclinical model of CNS lymphoma
Author: Christina A. von Roemeling, Ph.D., Research Associate, UF Brain Tumor Immunotherapy Program, Department of Neurosurgery, McKnight Brain Institute, University of Florida
Poster Number: P243
Additional meeting information can be found on the AACR (Free AACR Whitepaper) website at:
View Source

The presentations will also be available under "Posters and Presentations" in the Pipeline: CA-4948 section of the Company’s website at www.curis.com

About CA-4948

CA-4948 is an IRAK4 kinase inhibitor and IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, which are frequently dysregulated in patients with AML and MDS. Third parties have recently discovered that the long form of IRAK4 (IRAK4-L) is oncogenic and preferentially expressed in over half of patients with AML and MDS. The overexpression of IRAK4-L is believed to be driven by a variety of factors, including specific spliceosome mutations such as SF3B1 and U2AF1.