On April 13, 2021 Sanofi (Euronext: SAN and NYSE: SNY) and Kiadis (Euronext Amsterdam and Brussels: KDS) reported that that a total of 95.03% of the Kiadis shares on a Fully Diluted basis have been tendered or irrevocably committed to be delivered to Sanofi at Settlement under the Offer by Sanofi (Press release, Sanofi, APR 13, 2021, View Source [SID1234577958]). Sanofi declares the Offer unconditional (doet gestand) now all Offer Conditions described in the Offer Memorandum have either been satisfied or waived. As a result of the adoption of the Post-Offer Restructuring Resolution at the Kiadis extraordinary meeting of shareholders ("EGM") of 30 March 2021, under the terms and subject to the conditions of the Offer, the Acceptance Threshold is 80% (and not 95%) of Kiadis’ aggregate issued and outstanding ordinary share capital on a Fully Diluted basis, as of the time and date on which the Offer expires.

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!

Acceptance
During the Acceptance Period, that expired at 17:40 (CET) on 12 April 2021, 39,860,388 Shares were tendered under the Offer, representing approximately 92.9% of the aggregate issued and outstanding ordinary share capital of Kiadis as of today and an aggregate value of approximately
EUR 217,239,114.60 (for an Offer Price of EUR 5.45 (cum dividend) per Share). Together with any Shares directly or indirectly owned by Sanofi, the Offeror or any of their Affiliates, any Shares irrevocably committed to be delivered to Sanofi at settlement of the Offer and any Shares to which the Offeror Group is entitled but which have not yet been delivered (gekocht maar nog niet geleverd), this represents a total of 58,051,156 Shares. This equals approximately 95.03% of the aggregate issued and outstanding ordinary share capital of Kiadis on a Fully Diluted basis.

Settlement
With reference to the Offer Memorandum, Shareholders who accepted the Offer shall receive the Offer Price for each Tendered Share tendered during the Acceptance Period and transferred (geleverd) for acceptance pursuant to the Offer, under the terms and conditions of the Offer and subject to its restrictions.

Settlement of the Shares and payment of the Offer Price will take place on 16 April 2021. Following Settlement, the Offeror will (directly or indirectly) hold 58,051,156 Shares, representing approximately 95.03% of the aggregate issued and outstanding ordinary share capital of Kiadis on a Fully Diluted basis.

Upon Settlement the changes to the composition of the Supervisory Board and Management Board of Kiadis, as approved by the EGM on 30 March 2021, will become effective.

Post-Closing Acceptance Period
The Offeror hereby announces that Shareholders who have not tendered their Shares during the Acceptance Period will have the opportunity to tender their Shares under the same terms and conditions applicable to the Offer, during the Post-Closing Acceptance Period which will start at 09:00 (CET) on 14 April 2021 and end at 17:40 (CET) on 28 April 2021 (the "Post-Closing Acceptance Period").

The Offeror will publicly announce the results of the Post-Closing Acceptance Period and the total number and total percentage of Shares held by it in accordance with Section 17, paragraph 4 of the Decree ultimately on the third Business Day following the last day of the Post-Closing Acceptance Period.

The Offeror shall continue to accept for payment all Shares validly tendered (or defectively tendered provided that such defect has been waived by the Offeror) during the Post-Closing Acceptance Period and shall pay for such Shares as soon as reasonably possible and in any case no later than on the fifth Business Day following the last day of the Post-Closing Acceptance Period.

During the Post-Closing Acceptance Period, Shareholders have no right to withdraw Shares from the Offer, regardless of whether their Shares have been validly tendered (or defectively tendered, provided that such defect has been waived by the Offeror) during the Offer Period or the Post-Closing Acceptance Period.

Delisting
The Offeror and Kiadis shall seek to procure the delisting of the Shares on Euronext Amsterdam and Euronext Brussels as soon as possible under Applicable Rules. Delisting may further adversely affect the liquidity and market value of any Shares not tendered.

Further implications of the Offer being declared unconditional
Remaining Shareholders who do not wish to tender their Shares in the Post-Closing Acceptance Period should carefully review the sections of the Offer Memorandum that further explain the intentions of the Offeror, such as (but not limited to) Section 6.11 (Consequences of the Offer for non-tendering Shareholders), which describes certain implications to which such Shareholders may become subject with their continued shareholding in Kiadis.

The Offeror intends to initiate the Buy-Out in an expeditious manner. Reference is made to section 6.11(c) (Buy-Out) of the Offer Memorandum.

Announcements
Any announcement contemplated by the Offer Memorandum will be issued by press release. Any press release issued by the Offeror will be made available on the website of the Offeror (www.sanofi.com). Any press release issued by Kiadis will be made available on the website (www.kiadis.com).

Subject to any applicable requirements of the applicable rules and without limiting the manner in which the Offeror may choose to make any public announcement, the Offeror will have no obligation to communicate any public announcement other than as described above.

Offer Memorandum, Position Statement and further information
This announcement contains selected, condensed information regarding the Offer and does not replace the Offer Memorandum and/or the Position Statement. The information in this announcement is not complete and additional information is contained in the Offer Memorandum and the Position Statement.

Digital copies of the Offer Memorandum are available on the website of the Offeror (www.sanofi.com) and digital copies of the Position Statement are available on the website of Kiadis (www.kiadis.com). Such websites do not constitute part of, and are not incorporated by reference into, the Offer Memorandum. Copies of the Offer Memorandum and the Position Statement are on request also available free of charge at the offices of Kiadis and the Settlement Agent at the addresses below

On April 13, 2021 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a platform-driven, clinical-stage biopharmaceutical company committed to transforming the discovery and development of novel antibody-based immunotherapies, reported updated preclinical data from its lead SAFEbody program, ADG126, are being presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 (Press release, Adagene, APR 13, 2021, View Source [SID1234577961]).

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 critical unmet need for new anti-CTLA-4 therapies, and we are encouraged by the data generated to date, which demonstrate ADG126 has the potential to overcome the severe immune-mediated adverse reactions associated with the class," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. "By leveraging our SAFEbody platform technology, designed to precisely and very efficiently mask the antibody binding interface and activate specifically within the tumor microenvironment, our preclinical data continues to highlight the opportunity to effectively deliver treatment; ADG126 has demonstrated superior systemic safety profile at efficacious dose levels with a significantly enlarged therapeutic index (TI). Our ongoing global Phase 1 trial is expected to provide clinical validation for our SAFEbody platform and our SAFEbody product candidate, ADG126. We have successfully finished DLT evaluation of 3 patients at 0.1 mg/kg of ADG126 and remain on track to report topline safety and efficacy data in the second half of 2021."

A copy of the poster presentation, entitled "A Novel Anti-CTLA-4 Checkpoint Inhibitor Prodrug to Address On-target Off-tumor Toxicity for Cancer Immunotherapy," is available on the AACR (Free AACR Whitepaper) website and is also available for download via our website (View Source).

The data presented show:

Notable Findings: ADG126 demonstrated an impressive safety margin while maintaining its potent antitumor activity.
Unique Epitope with Broad Species Cross-Reactivity: ADG126 targets a conserved epitope of CTLA-4 with broad species cross-reactivity and is an activatable prodrug for tumor suppression in multiple syngeneic mouse models in single and combination therapies.
Differentiated Mechanism of Action: Although the activated ADG126 is softer in blocking CTLA-4 binding with its ligands than ipilimumab, the activated ADG126 exhibited more potent antibody dependent cellular cytotoxicity (ADCC) in the tumor microenvironment.
Intra-Tumoral Treg Depletion: Treg cells in tumor tissues exhibited higher CTLA-4 expression than in peripheral tissues and were efficiently depleted upon treatment with ADG126 in the immune-competent mouse syngeneic colon tumor model.
Human T-Cell Activation in Vitro: Activated ADG126 potently enhanced T-cell activation, measured by IL-2 secretion, whereas the masked ADG126 did not.
In Vivo Monotherapy Antitumor Activity: ADG126 exhibited potent antitumor activity as a single agent in different immune-competent syngeneic mouse tumor models.
In Vivo Combination Antitumor Activity: ADG126 combined synergistically with other IO agents, such as anti-PD-1 antibody, to inhibit tumor growth in vivo. Combination therapy significantly slowed tumor growth and caused complete regression in 50% of Lewis lung cancer mouse models.
Safety and Tolerability: ADG126 was well tolerated in animals suggesting the potential for high therapeutic index. The highest non-severely toxic dose (HNSTD) was determined to be 200 mg/kg/dose, which is one of the highest reported HNSTD for anti-CTLA-4 antibodies.
About ADG126
ADG126 is a fully human antagonistic mAb targeting a novel epitope of CTLA-4 and has been shown to specifically deplete regulatory T-cells in tumors. ADG126 is Adagene’s lead SAFEbody product candidate. The SAFEbody technology, developed using Adagene’s AI-powered platform, enables binding of an antibody to a specific target only after conditional activation of the antibody in target tissues.

In preclinical studies, ADG126 was well tolerated in cynomolgus monkeys and demonstrated an encouraging antitumor response in multiple immune-competent mouse tumor models in a dose-dependent manner both as a single agent and in combination with anti-PD-1 and other therapies.

Unlike anti-PD-1/PD-L1 check point inhibitors, anti-CTLA-4 is known for its dose-dependent clinical response in single and combination therapies, which is severely limited by the narrow therapeutic window available to current anti-CTLA-4 therapies. The large safety margin shown by ADG126 GLP toxicology studies of up to 200 mg/kg in targeting CTLA-4 will make it possible to dose patients for their optimal clinical benefits in single and combination therapies.

On April 13, 2021 Nurix Therapeutics Inc. (Nasdaq: NRIX), a biopharmaceutical company developing targeted protein modulation drugs, reported financial results for the first quarter ended February 28, 2021 and provided a corporate update (Press release, Nurix Therapeutics, APR 13, 2021, View Source [SID1234577979]).

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!

"We began 2021 with the initiation of our first clinical trial to evaluate NX-2127, an orally available degrader of Bruton’s tyrosine kinase with immunomodulatory drug activity in patients with relapsed or refractory B-cell malignancies," said Dr. Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "We are on track to initiate Phase 1 trials for three more proprietary drug candidates in 2021 for patients with hematologic malignancies and solid tumors."

Recent Business Highlights

Expanded Strategic Collaboration with Sanofi S.A. (Sanofi): On January 7, 2021, Nurix announced the expansion of its global strategic collaboration with Sanofi to discover, develop and commercialize a pipeline of innovative targeted protein degradation drugs for patients with challenging diseases in multiple therapeutic areas. Sanofi has exercised its option to expand the number of targets in the collaboration agreement from three to a total of five targets. With the expansion, Nurix received a payment of $22 million, in addition to the previously received upfront payment of $55 million.
Completed a Public Follow-on Offering: On March 9, 2021, Nurix announced the closing of its underwritten public offering of 5,175,000 shares of common stock, at a public offering price of $31.00 per share, which included 675,000 shares issued upon the exercise in full by the underwriters of their option to purchase additional shares of common stock. The net proceeds to Nurix from the offering were approximately $150 million, after deducting underwriting discounts, commissions and offering expenses.
Presented Preclinical Data Highlighting NX-1607: Nurix presented data from its NX-1607 program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2021 annual meeting which is being held virtually over two weeks, April 10-15 and May 17-21. NX-1607, an orally bioavailable, small-molecule inhibitor of Casitas B-lineage lymphoma B (CBL-B), demonstrated significant anti-tumor efficacy in animal models of both colorectal cancer and triple negative breast cancer. Importantly, the combination of NX-1607 and an anti-PD-1 antibody substantially increased the median overall survival and the frequency of long-lasting tumor rejection in these models compared to either single agent alone. The activity of NX-1607 was shown to be dependent on CD8+ T cells and NK cells. A copy of the poster can be found on Nurix’s website (link).
Announced Collaboration for the Discovery of Novel Drugs to Treat Pediatric Cancers: On March 16, 2021, Nurix announced that it is part of a collaboration sponsored by Alex’s Lemonade Stand Foundation (ALSF), a leading funder of pediatric cancer research, to develop a drug to potentially treat aggressive childhood cancers including neuroblastoma and medulloblastoma. Nurix will provide its extensive expertise in E3 ligases and use its proprietary DNA-encoded library to help identify small-molecule degraders of MYCN, a target previously considered undruggable. The program is one of four that are being supported by ALFS’s Crazy 8 initiative, which is designed to bring together world-class research talent to accelerate the pace of new cure discovery in childhood cancer.
Upcoming Program Highlights

NX-2127: Nurix’s lead drug candidate from its protein degradation portfolio, NX-2127, is an orally available degrader of Bruton’s tyrosine kinase (BTK) with immunomodulatory drug (IMiD) activity for the treatment of relapsed or refractory B-cell malignancies. Nurix filed an IND for NX-2127 in December 2020 and received clearance by the U.S. FDA to initiate human clinical trials. Clinical sites are actively recruiting patients for a Phase 1 clinical trial of NX-2127. Additional information on the clinical trial can be accessed at ClinicalTrials.gov (NCT04830137).
NX-1607: Nurix’s lead drug candidate from its E3 ligase inhibitor portfolio, NX-1607, is an orally available inhibitor of CBL-B for immuno-oncology indications. Nurix anticipates initiating a Phase 1 trial for NX-1607 in the second half of 2021 (expected timing of events here and throughout the press release are based on calendar year quarters).
NX-5948: Nurix’s second drug candidate from its protein degradation portfolio, NX-5948, is an orally available BTK degrader designed without IMiD activity for certain B-cell malignancies, autoimmune diseases and related diseases such as graft-versus-host disease. Nurix recently disclosed that NX-5948 crosses the blood brain barrier in animal models, further differentiating it from NX-2127. NX-5948 has also demonstrated potent anti-inflammatory activity in an animal model of rheumatoid arthritis. Nurix anticipates initiating a Phase 1 trial for NX-5948 in patients with hematologic malignancies in the second half of 2021.
DeTIL-0255: Nurix’s lead candidate in its cellular therapy portfolio, DeTIL-0255, is a drug-enhanced adoptive cellular therapy. Nurix anticipates initiating a Phase 1 trial for DeTIL-0255 in the second half of 2021.
Fiscal First Quarter 2021 Financial Highlights

Collaboration revenue for the three months ended February 28, 2021 was $5.0 million compared to $2.9 million for the three months ended February 29, 2020. The increase was primarily due to our collaboration with Sanofi, which continued to scale up resources as compared to the prior period, resulting in higher revenue recognition due to a higher percentage of completion in the current period.

Research and development expenses for the three months ended February 28, 2021 were $23.0 million compared to $13.0 million for the three months ended February 29, 2020. The increase was primarily related to an increase of $4.6 million in compensation and related personnel costs attributable to an increase in headcount and higher non-cash stock-based compensation expense. There was also an increase of $3.5 million attributable to increases in preclinical development activities and drug discovery research and an increase of $1.1 million due to preparation for upcoming clinical activities.

General and administrative expenses for the three months ended February 28, 2021 were $6.5 million compared to $2.5 million for the three months ended February 29, 2020. The increase was primarily related to an increase of $2.4 million in compensation related expenses attributable to a higher headcount and includes $1.4 million of higher non-cash stock-based compensation expense and an increase of $1.0 million in consultant and other professional service expenses primarily related to becoming a public company.

Net loss attributed to common stockholders for the three months ended February 28, 2021 was $24.3 million, or ($0.63) per share, compared to a net loss of $12.4 million, or ($3.50) per share, for the three months ended February 29, 2020.

Cash, Cash Equivalents and Investments: As of February 28, 2021, Nurix had cash, cash equivalents and investments of $380.3 million compared to $372.0 million as of November 30, 2020. Including net proceeds of $150.1 million from the recently completed follow-on offering, Nurix has proforma cash, cash equivalents and investments of $530.4 million.

On April 13, 2021 Qilu Puget Sound Biotherapeutic Corp. (Sound Biologics), an emerging biotechnology company focused on developing a novel MabPair platform for antibody-based combination therapies for the treatment of cancer, inflammation and autoimmune disease, reported a clinical update on its first MabPair product PSB205 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Sound Biologics, APR 13, 2021, View Source [SID1234577995]). Dr Li Zhang of Sun Yat-Sen University Cancer Centre (SYSUCC), Guangzhou, China presented a poster on Phase 1 Clinical Trial results of PSB205, a combination of anti-PD1 and anti-CTLA-4 antibodies that are manufactured together as a single product, in patients with advanced malignant tumors. The study is sponsored by Qilu Pharma in China.

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!

Details of the presentation:

Presentation Title: Development and Preliminary Clinical Activity of QL1706 (PSB205), a Combination of anti-PD1 and anti-CTLA-4 Antibodies Manufactured Together as a Single Product

Session Title/Category: Phase I Clinical Trials

Session Type: E-Poster Session, 8:30 AM – 11:59 PM, Saturday, April 10

Poster Number: CT119

Forty-seven patients, 95% of whom had refractory Naso-Pharyngeal (NPC) or lung (NSCLC) cancers, were enrolled at a single clinic with over 5 ascending dose levels in a standard 3+3 design. A dose of 5 mg/kg was selected for continued clinical development. The most common side effects were Grade 1 pruritus and rash. Dose-limiting immune-related reactions occurred only at doses higher than 5 mg/kg. The Overall Rate of Response (ORR) was 29% among 35 patients evaluable for tumor response; among 20 patients without prior exposure to checkpoint-targeted immunotherapy, 40 % achieved Partial Response (PR), whereas 2 of 10 patients (20%) previously treated and progressed on earlier immunotherapy realized PR. For 5 patients on study, pre-study checkpoint inhibitor exposure status was unknown due to earlier participation in a still-blinded randomized immunotherapy trial.

"The Phase 1 data presented at AACR (Free AACR Whitepaper) provides encouraging proof-of-concept and early clinical validation of the MabPair platform," commented Sound Biologics’ Chief Executive Officer Wei Yan, PhD. "The early data offer multiple opportunities for further development of this dual immune checkpoint blockade product."

About PSB205

PSB205 is a first-in-class bifunctional product that contains a mixture of unique anti-PD-1 and anti-CTLA-4 monoclonal antibodies produced by a single cell line via the company’s proprietary MabPairTM technology. MabPair products offer many advantages over bispecific antibodies. The relative ratio of the two antibodies in the MabPair can be well controlled, and each antibody is individually engineered for optimal target coverage, effector function, pharmacokinetics and exposure. The anti-CTLA-4 component of the MabPair is designed with a shorter half-life than currently available anti-CTLA-4 antibodies in an effort to reduce known side effects associated with CTLA-4 blockade. Preclinical studies with PSB205 demonstrated superior efficacy in tumor models compared to either checkpoint inhibitor alone. PSB205 represents a potentially best-in-class immuno-oncology product that promises to exhibit robust combination activity while being significantly more tolerable to patients than currently approved anti-PD-1/anti-CTLA-4 combinations. Parallel Phase 1 studies in a broad range of refractory solid tumors are currently ongoing in China and the United States (www.clinicaltrials.gov; NCT03986606), and the AACR (Free AACR Whitepaper) poster represents the first release of clinical data from one of these studies.

On April 13, 2021 Arcellx, a privately held clinical-stage biopharmaceutical company, reported that it raised $115 million in a Series C financing to advance its pipeline of adaptive and controllable cell therapies (Press release, Arcellx, APR 13, 2021, View Source [SID1234577962]). The proceeds will support the company’s development of CART-ddBCMA, a BCMA-specific CAR-modified T-cell therapy currently in Phase 1 and anticipated to begin a pivotal trial in 2022. In addition, the funding will support initiation of clinical trials evaluating ACLX-001 and ACLX-002, cell therapies derived from Arcellx’s uniquely controllable ARC-SparX platform, in multiple myeloma (MM) and acute myelogenous leukemia (AML), respectively.

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 financing follows FDA clearance of Arcellx’s IND for ACLX-001, the first ARC-SparX program to enter clinical trials, and Arcellx’s initial release of clinical results at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) meeting. In the ASH (Free ASH Whitepaper) release, the CART-ddBCMA data showed all six multiple myeloma patients responded per IMWG criteria, with four of those patients achieving stringent complete response. The therapy was also well-tolerated, and CAR-T related toxicities resolved rapidly.

Participants in the Series C financing include both existing and new investors to Arcellx. The financing was co-led by Samsara BioCapital and CAM Capital, joined by new investors Adage, Asymmetry, CaaS Capital, Cambrian Bio, Sixty Degree, Soleus Capital, Surveyor Capital (a Citadel company), Suvretta, and Terra Magnum Capital Partners, and existing investors NEA, Novo Holdings, SR One, Takeda Ventures, LG Tech, and Clough Capital.

"With support from this high caliber syndicate, Arcellx is poised to elevate the field of cell therapy by advancing our treatments for a range of cancers," said Rami Elghandour, Chairman and Chief Executive Officer of Arcellx. "Our platform of both single infusion and controllable CAR-Ts based on our novel synthetic binding domain is built to address the limitations of cell therapy with the opportunity to improve efficacy, reduce toxicity, and shorten the time to intervention while expanding into new indications. This financing positions us to advance to a registrational study in multiple myeloma and to initiate a Phase 1 study in AML in 2022 as well as progress our solid tumor targets toward the clinic. It’s also a reflection of our incredibly talented and diverse team that is powering Arcellx forward. We appreciate the support of our new and existing investors as we advance our novel therapies to the benefit of cancer patients most in need."

"Based on the early clinical data, we believe that CART-ddBCMA represents a potential best-in class therapy for multiple myeloma and with the support of this financing will be positioned to move into pivotal trials next year. We’re also excited about the opportunity for CART-ddBCMA to move into earlier lines of treatment for multiple myeloma based on the safety profile in this early data set. In addition, the ARC-SparX platform will be the first adaptive and controllable CAR-T system to enter the clinic and provides a unique approach to building next generation cell therapies. We look forward to partnering with the Arcellx team to help bring these important therapies to patients," said Mike Dybbs, Ph.D., Partner, Samsara BioCapital.