Biohaven acquisition of Pyramid Biosciences

On March 12, 2024 Biohaven Pharmaceutical has acted as counsel as to British Virgin Islands law to the Company in respect of the proposed resale of an aggregate of 45,883 common shares in the Company with no par value (the "Shares") issued on 7 January 2024 and 8 March 2024 to the Selling Shareholders (as defined in the Prospectus Supplement) pursuant to the terms of an Agreement and Plan of Merger dated 7 January 2024 entered into between the Company, Adjo Sub, Inc., Pyramid Biosciences, Inc. and Shareholder Representative Services LLC (the "Agreement") (Press release, Biohaven Pharmaceutical, MAR 12, 2024, View Source [SID1234644166]). We have been asked to provide this legal opinion in connection with the Company’s registration statement on Form S-3, including all amendments or supplements thereto, and the prospectus supplement dated 12 March 2024 (the "Prospectus Supplement") filed with the United States Securities and Exchange Commission (the "Commission") under the United States Securities Act of 1933, as amended (the "SEC Act") (the "Registration Statement").
1Documents Reviewed
We have reviewed originals, copies, drafts or conformed copies of the following documents:
1.1The public records of the Company on file and available for public inspection at the Registry of Corporate Affairs in the British Virgin Islands (the "Registry of Corporate Affairs") on 12 March 2024, including the Company’s Certificate of Incorporation and its Memorandum and Articles of Association (the "Memorandum and Articles").
1.2The records of proceedings available from a search of the electronic records maintained on the Judicial Enforcement Management System from 1 January 2000 and available for inspection on 12 March 2024 at the British Virgin Islands High Court Registry (the "High Court Registry").
1.3The written resolutions of the board of directors passed on 31 December 2023 and 10 March 2024 (the "Resolutions").
1.4A Certificate of Incumbency dated 11 March 2024, issued by Maples Corporate Services (BVI) Limited, the Company’s registered agent (the "Registered Agent’s Certificate").
1.5A certificate of good standing with respect to the Company issued by the Registrar of Corporate Affairs dated 11 March 2024 (the "Certificate of Good Standing").
1.6A certificate from a director of the Company (the "Director’s Certificate").
1.7The Registration Statement.

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2Assumptions
The following opinions are given only as to, and based on, circumstances and matters of fact existing and known to us on the date of this opinion letter. These opinions only relate to the laws of the British Virgin Islands which are in force on the date of this opinion letter. In giving the following opinions we have relied (without further verification) upon the completeness and accuracy, as at the date of this opinion letter, of the Registered Agent’s Certificate, the Certificate of Good Standing and the Director’s Certificate. We have also relied upon the following assumptions, which we have not independently verified:
2.1The Agreement was and is authorised and duly executed and unconditionally delivered by or on behalf of all relevant parties in accordance with all relevant laws (including, without limitation, the laws of the British Virgin Islands).
2.2The Agreement was and is legal, valid, binding and enforceable against all relevant parties in accordance with its terms under all relevant laws (including, without limitation, the laws of the British Virgin Islands).
2.3Copies of documents, conformed copies or drafts of documents provided to us are true and complete copies of, or in the final forms of, the originals.
2.4All signatures, initials and seals are genuine.
2.5That all public records of the Company which we have examined are accurate and that the information disclosed by the searches which we conducted against the Company at the Registry of Corporate Affairs and the High Court Registry is true and complete and that such information has not since then been altered and that such searches did not fail to disclose any information which had been delivered for registration but did not appear on the public records at the date of our searches.
2.6The Memorandum and Articles remain in full force and effect and are unamended and that there are a sufficient number of authorised shares to allow for the issuance of the Shares.
2.7The Resolutions were each signed by all the directors in the manner prescribed in the Memorandum and Articles of the Company, including as to the disclosure of any director’s interests, and have not been amended, varied or revoked in any respect.
2.8The members of the Company (the "Members") have not restricted or limited the powers of the directors of the Company in any way.
2.9No invitation has been or will be made by or on behalf of the Company to the public in the British Virgin Islands to subscribe for any of the Shares.
2.10The Shares issued pursuant to the Agreement have been, or will be, duly registered, and will continue to be registered, in the Company’s register of members.
2.11The Company has received, or will receive, cash consideration or non-cash consideration in consideration for the issue of the Shares, and that:
(a) none of the Shares have been, or will be, issued for less than their par value; and
(b) to the extent that any Shares are, or will be, issued, in whole or in part, for non-cash consideration, the value of the non-cash consideration and cash consideration, if any, is not less than the amount credited or to be credited for such Shares.
2.12The issue of the Shares to the Selling Shareholder by the Company as contemplated by the Agreement, as applicable, was authorised and such Shares were legally issued, fully paid and non-assessable (as a matter of all relevant laws, other than the laws of the British Virgin Islands) and all conditions to the issuance of the Shares pursuant to the Agreement were satisfied.
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2.13There is nothing under any law (other than the laws of the British Virgin Islands) which would or might affect the opinions set out below.
Save as aforesaid we have not been instructed to undertake and have not undertaken any further enquiry or due diligence in relation to the transaction the subject of this opinion.
3Opinions
Based upon, and subject to, the foregoing assumptions and the qualifications set out below, and having regard to such legal considerations as we deem relevant, we are of the opinion that:
3.1The Shares held by the Selling Shareholder to be resold as contemplated by the Registration Statement were duly authorised, and when issued and paid for in the manner described in the Agreement and in accordance with the Resolutions, such Shares were legally issued, fully paid and non-assessable. As a matter of British Virgin Islands law, a share is only issued when it has been entered in the register of members of the Company.
4Qualifications
The opinions expressed above are subject to the following qualifications:
4.1We have not reviewed the Agreement save as expressly referred to in paragraph 3.1 of this opinion and our opinions are qualified accordingly.
4.2We express no view as to the commercial terms of the Agreement or whether such terms represent the intentions of the parties and we make no comment with respect to any representations and warranties which may be made by or with respect to the Company in any of the documents or instruments cited in this opinion or otherwise with respect to the commercial terms of the transactions the subject of this opinion.
4.3Under British Virgin Islands law, the register of members is prima facie evidence of title to shares and this register would not record a third party interest in such shares. However, there are certain limited circumstances where an application may be made to a British Virgin Islands court for a determination on whether the register of members reflects the correct legal position. Further, the British Virgin Islands court has the power to order that the register of members maintained by a company should be rectified where it considers that the register of members does not reflect the correct legal position. For the purposes of the opinion given in paragraph 3.1, there are no circumstances or matters of fact known to us on the date of this opinion letter which would properly form the basis for an application for an order for rectification of the register of members of the Company, but if such an application were made in respect of the Company’s Shares, then the validity of such shares may be subject to re-examination by a British Virgin Islands court.
4.4Except as specifically stated herein, we make no comment with respect to any representations and warranties which may be made by or with respect to the Company in any of the documents or instruments cited in this opinion or otherwise with respect to the commercial terms of the transactions the subject of this opinion.
4.5In this opinion letter, the phrase "non-assessable" means, with respect to the issuance of shares, that a shareholder shall not, in respect of the relevant shares and in the absence of a contractual arrangement, or an obligation pursuant to the memorandum and articles of association, to the contrary, have any obligation to make further contributions to the Company’s assets (except in exceptional circumstances, such as involving fraud, the establishment of an agency relationship or an illegal or improper purpose or other circumstances in which a court may be prepared to pierce or lift the corporate veil).
We hereby consent to the filing of this opinion as an exhibit to the Registration Statement and to the reference to our firm under the heading "Validity of Securities" in the prospectus included in the Registration Statement. In providing our consent, we do not thereby admit that we are in the category of persons whose consent is required under Section 7 of the SEC Act or the rules and regulations of the Commission thereunder.
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This opinion is addressed to you and may be relied upon by you, your counsel and purchasers of Shares pursuant to the Registration Statement. This opinion is limited to the matters detailed herein and is not to be read as an opinion with respect to any other matter.

Pearl Bio Inks Collaboration with Merck to Discover Novel Engineered Biologics

On March 12, 2024 Pearl Bio (a synthetic biology company backed by Khosla Ventures) reported that it has entered a license, collaboration and option agreement with Merck, known as MSD outside of the United States and Canada, to discover biologic therapies comprising non-standard amino acids (Press release, Pearl Bio, MAR 12, 2024, View Source [SID1234641089]). Bolstering this collaboration is the deep expertise and patent portfolio licensed from the labs of scientific co-founders, Farren Isaacs (Yale) and Michael Jewett (Stanford) for using Genomically Recoded Organisms (GROs) to encode synthetic chemistries, paving the road for entirely new classes of multi-functionalized biologics with tunable properties.

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The Pearl team is excited to leverage our blocking IP on genome recoding and translation engineering to advance novel biologics with synthetic amino acids in partnership with Merck.

The collaboration will initially focus on discovery and development of biologic therapies for the treatment of cancer leveraging Pearl’s exclusive GRO technology, unique ability to work in both cell-based and cell-free systems and proprietary tethered ribosomes to encode synthetic monomers and target previously inaccessible epitopes.

"We are excited to demonstrate the power of Pearl’s technology in our partnership with Merck to create multi-functionalized therapeutic candidates with tunable properties solving for some of the key shortcomings confronting biologics," explained Co-Founder and President, Amy Cayne Schwartz.

Under the agreement, Pearl is eligible to receive payments totaling up to $1B across upfront, option and milestone payments in addition to potential royalties on sales of approved products derived from the collaboration.

"Merck is excited to collaborate with Pearl, a pioneer in developing recoded organisms, to produce novel biologics enabled by synthetic chemistries," shared Juan Alvarez, Vice President of Discovery Biologics at Merck Research Laboratories.

Natera to Present New Data at the 2024 SGO Annual Meeting on Women’s Cancer, Following Recent Medicare Coverage Decisions in Ovarian and Breast Cancers

On March 12, 2024 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, reported new data being presented on its personalized and tumor-informed molecular residual disease (MRD) test, Signatera, and hereditary cancer test, Empower, at the 2024 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer taking place March 16-18, 2024 (Press release, Natera, MAR 12, 2024, View Source [SID1234641088]).

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A total of seven abstracts will be presented, including two oral presentations and five poster presentations. The presentations will feature new data highlighting Signatera’s predictive and prognostic utility in ovarian cancer and other gynecologic malignancies.

"On the heels of receiving Medicare coverage for Signatera in ovarian cancer and for breast cancer in the neoadjuvant setting, we are thrilled to share new Signatera and Empower data with the gynecologic oncology community," said Adam ElNaggar, MD, medical director of oncology at Natera. "We believe this momentum is indicative of the growing clinical value our tests provide for patients across the continuum of gynecologic cancer care, and demonstrate our continued leadership in MRD."

Below is the full list of Signatera and Empower data presentations at the SGO Annual Meeting.

Oral Presentations:

Focused Plenary I: The Science to Drive Purpose | March 16, 2:15 – 3:30 PM | Presenter: Anne Knisely, MD | Ovarian Cancer
Prognostic implications of minimal residual disease detection by second look laparoscopy and circulating tumor DNA (ctDNA) in patients with ovarian cancer after frontline therapy
Focused Plenary IV: ctDNA: Molecular Mirrors & Markers | March 17, 1:45 – 2:45 PM | Presenter: Mike Shalamov | Gynecologic Cancers
Utility of ctDNA as an early predictive biomarker of response to radiation in gynecologic malignancies
Poster Presentations:

Poster #1241 | Session 1 | March 17, 1:15 – 2:45 PM | Presenter: Michael Toboni, MD | Ovarian Cancer
PARPi response monitoring using personalized ctDNA testing in patients with ovarian cancer
Poster #1242 | Session 1 | March 17, 1:15 – 2:45 PM | Presenter: Peter W. Ketch, MD | Uterine Cancer
Treatment Monitoring Utilizing ctDNA-based MRD Detection in Early Stage Uterine Cancer
Poster #1243 | Session 1 | March 17, 1:15 – 2:45 PM | Presenter: Michael Toboni, MD | Uterine Cancer
Personalized ctDNA analysis used for ctDNA detection and response monitoring in patients with advanced or recurrent uterine cancer
Poster #1274 | Session 1 | March 17, 1:15 – 2:45 PM | Presenter: Floortje Backes, MD | Endometrial and Ovarian Cancer
Utility of ctDNA in assessment of treatment response in patients with Recurrent/Metastatic Endometrial Cancer and Recurrent/Platinum-Resistant Ovarian Cancer
Poster #1181 | Session 1 | March 17, 1:15 – 2:45 PM | Presenter: Sarah Lee, MD | Pan-cancer
Diagnostic yield and characteristics of germline-positive genetic testing ordered by obstetricians and gynecologists in female patients with a personal history of cancer
About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer, ovarian cancer and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 50 peer-reviewed papers.

SOTIO Presents New Preclinical Data on Enhanced CAR T-Cell Therapies at AACR Annual Meeting

On March 12, 2024 SOTIO Biotech, a clinical-stage immuno-oncology company owned by PPF Group, reported it will present new preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 5-10, 2024, in San Diego, California (Press release, SOTIO, MAR 12, 2024, View Source [SID1234641087]).

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In a poster at the conference, SOTIO will present data from the company’s BOXR platform of enhanced T cell therapies. SOTIO leveraged the BOXR technology to design CAR T cells enhanced with transgenes encoding GOT2 (glutamine oxaloacetate transaminase) and TIGAR (TP53-induced glycolysis and apoptosis regulator), both of which are believed to play a role in T cell fitness in the hostile solid tumor microenvironment. Compared to unmodified CAR T cells and CAR T cells enhanced with GOT2 solely, CAR T cells enhanced with GOT2 and TIGAR showed better tumor infiltration, lower levels of exhaustion, and superior anti-tumor activity in a mouse model of solid tumors.

SOTIO’s lead candidate from the BOXR platform, BOXR1030 — a GOT2-enhanced CAR T-cell therapy — is currently being evaluated in a Phase 1/2 study for patients with solid tumors.

A second study to be presented at the meeting investigated the immunostimulatory effects of PARP inhibitors in models of epithelial ovarian cancer, determining their activity on molecular and cellular pathways to inform better combination therapy strategies with cancer immunotherapies.

Poster details are as follows:

Title: "Dual expression of exogenous glutamine oxaloacetate transaminase (GOT2) and TP53-induced glycolysis and apoptosis regulator (TIGAR) enhance CAR T cell activity in preclinical solid tumor models"
Presenting Author: Amy Jensen-Smith
Abstract Number: 4012
Date & Time: April 9, 2024, 9:00 a.m. – 12:30 p.m. PT

Title: "Immunological control by PARP inhibitors for successful immunotherapy in metastatic ovarian carcinoma"
Presenting Author: Peter Holicek
Abstract Number: 5278
Date & Time: April 9, 2024, 1:30 p.m. – 5:00 p.m. PT

Presentation materials will be available after presentations conclude here.

Nutcracker Therapeutics to Present Data on mRNA Drug Candidate and Immunomodulatory Cytokine at AACR 2024

On March 12, 2024 Nutcracker Therapeutics, Inc., a biotechnology company dedicated to developing transformative RNA therapies through its proprietary technology platform, reported that two poster presentations highlighting the company’s RNA therapeutics pipeline will be introduced at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Nutcracker Therapeutics, MAR 12, 2024, View Source [SID1234641086]).

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The first presentation entails LIGHT, an immunomodulatory cytokine that is one of the components of NTX-250, the company’s lead candidate for cervical intraepithelial neoplasia. The second presentation is on preclinical data for Nutcracker’s mRNA drug candidate for prostate cancer, NTX-470. This therapy is designed to target prostate cancer antigens with mRNA-encoded, multi-specific T cell engagers with a strong anti-tumor effect and low toxicity.

Poster Presentations at AACR (Free AACR Whitepaper) 2024

Title: NTX-470, a novel multispecific T cell engager expressed from mRNA targets PSMA and STEAP1 prostate cancer antigens to generate enhanced functional activity
Abstract Number: 6725
Session Title: Targeted Immune Cell Engagers
Session Date and Time: April 10, 2024, 9:00 a.m. to 12:30 p.m.
Lead Author: Chris Rae

Title: Enhanced membrane stability of mRNA nanoparticle derived TNFSF14 results in superior T- cell and NK cell stimulation
Abstract Number: 6536
Session Title: Tumor Microenvironment and Cancer Immunity
Session Date and Time: April 9, 2024, 1:30 p.m. to 5:00 p.m.
Lead Author: Adrienne Sallets

The 2024 AACR (Free AACR Whitepaper) Annual Meeting takes place in San Diego from April 5-10. Full abstracts are available on the AACR (Free AACR Whitepaper) Online Program Planner. More information about the conference can be found on AACR (Free AACR Whitepaper)’s website.