UNITED STATES
SECURITIES AND EXCHANGE
COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13
or 15(d) of the Securities Exchange Act of 1934
Date of Report
(Date of earliest event reported): July 29,
2024
Chain Bridge I
(Exact name of registrant
as specified in its charter)
| Cayman Islands |
|
001-41047 |
|
98-1578955 |
(State or other jurisdiction of
incorporation) |
|
(Commission File Number) |
|
(I.R.S. Employer
Identification No.) |
|
8
The Green #17538
Dover, DE |
|
19901 |
| (Address of principal executive
offices) |
|
(Zip Code) |
(202) 656-4257
(Registrant’s
telephone number, including area code)
Not Applicable
(Former name or former
address, if changed since last report)
Check the appropriate
box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the Registrant under any of the following
provisions:
| x |
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ¨ |
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ¨ |
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ¨ |
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of
the Act:
| Title of each class |
|
Trading
Symbol(s) |
|
Name
of each exchange
on which registered |
| Units,
each consisting of one Class A ordinary share and one-half of one redeemable warrant to acquire one Class A ordinary share |
|
CBRGU |
|
The
Nasdaq
Capital Market |
| Class
A ordinary shares, par value $0.0001 per share |
|
CBRG |
|
The
Nasdaq
Capital Market |
Indicate by check mark whether the registrant
is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 or Rule 12b-2 of the Securities
Exchange Act of 1934.
Emerging
growth company x
If
an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying
with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨
| Item 7.01 |
Regulation FD Disclosure. |
As previously announced, on
July 22, 2024, Chain Bridge I, a Cayman Islands exempted company (“CBRG”), CB Holdings, Inc., a Nevada corporation (“HoldCo”),
CB Merger Sub 1, a Cayman Islands exempted company (“CBRG Merger Sub”), Phytanix Bio, a Nevada corporation (the “Company”),
and CB Merger Sub 2, Inc., a Nevada corporation (“Company Merger Sub”), entered into a Business Combination Agreement (as
it may be amended, supplemented or otherwise modified from time to time, the “Business Combination Agreement”). Furnished
herewith as Exhibit 99.1 and incorporated into this Item 7.01 by reference, is an investor presentation, dated as of July 29, 2024, that
CBRG, the Company and HoldCo have prepared for use in connection with the Business Combination and various meetings with investors.
The foregoing (including Exhibit
99.1) is being furnished pursuant to Item 7.01 and will not be deemed to be filed for purposes of Section 18 of the Securities and Exchange
Act of 1934, as amended (the “Exchange Act”), or otherwise be subject to the liabilities of that section, nor will it be deemed
to be incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act.
Forward-Looking Statements
Certain statements in this
Current Report may be considered “forward-looking statements” within the meaning of the “safe harbor” provisions
of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements generally relate to future events or
CBRG’s, the Company’s or HoldCo’s future financial or operating performance. For example, any statements that refer
to expectations, projections or other characterizations of future events or circumstances, including post-Business Combination fully diluted
equity value, the anticipated enterprise value of HoldCo, expected ownership in HoldCo, projections of market opportunity and market share,
the capability of the Company’s or HoldCo’s business plans including its plans to expand, the sources and uses of cash from
the Business Combination, any benefits of the Company’s partnerships, strategies or plans as they relate to the Business Combination,
anticipated benefits of the Business Combination and expectations related to the terms and timing of the Business Combination, the Company’s
expected pro forma cash, the Company’s or HoldCo’s expected cash runway through 2025 or statements related to the Company’s
or HoldCo’s funding gap, funded business plan or use of proceeds, or other metrics or statements derived therefrom, are forward-looking
statements. In some cases, you can identify forward-looking statements by terminology such as “anticipate,” “believe,”
“continue,” “could,” “estimate,” “expect,” “forecast,” “future,”
“intend,” “may,” “might,” “plan,” “possible,” “potential,” “predict,”
“project,” “propose,” “seek,” “should,” “strive,” “will,” or “would”
or the negatives of these terms or variations of them or similar terminology. Such forward-looking statements are subject to risks, uncertainties,
and other factors which may be beyond the control of CBRG, the Company or HoldCo and could cause actual results to differ materially from
those expressed or implied by such forward-looking statements. These forward-looking statements are based upon estimates and assumptions
that, while considered reasonable by CBRG and its management, the Company and its management and HoldCo and its management, as the case
may be, are inherently uncertain. Each of CBRG, the Company and HoldCo caution you that these statements are based on a combination of
facts and factors currently known and projections of the future, which are inherently uncertain. There will be risks and uncertainties
described in the proxy statement/prospectus included in the Registration Statement relating to the Business Combination, which is expected
to be filed by HoldCo with the SEC, and described in other documents filed by CBRG or HoldCo from time to time with the SEC. These filings
may identify and address other important risks and uncertainties that could cause actual events and results to differ materially from
those contained in the forward-looking statements. Neither CBRG nor the Company can assure you that the forward-looking statements in
this Current Report will prove to be accurate.
In addition, new risks and uncertainties may emerge
from time to time, and it may not be possible to identify and accurately predict the potential impacts of any such risks and uncertainties
that may arise in the future. Factors that may cause actual results to differ materially from current expectations include, but are not
limited to: (1) the occurrence of any event, change or other circumstances that could give rise to the termination of negotiations and
any subsequent definitive agreements with respect to the Business Combination; (2) the outcome of any potential litigation, government
or regulatory proceedings that may be instituted against CBRG, the Company, HoldCo or others; (3) the inability to complete the Business
Combination due to the failure to obtain approval of the shareholders of CBRG, to obtain financing to complete the Business Combination
or to satisfy other conditions to closing; (4) the amount of redemption requests made by CBRG’s public shareholders; (5) changes
to the proposed structure of the Business Combination that may be required or appropriate as a result of applicable laws or regulations
or as a condition to obtaining regulatory approval of the Business Combination; (6) delays in obtaining, adverse conditions in, or the
inability to obtain regulatory approvals, or delays in completing regulatory reviews, required to complete the Business Combination; (7)
the ability to meet stock exchange listing standards prior to or following the consummation of the Business Combination; (8) the risk
that the Business Combination disrupts current plans and operations of the Company or HoldCo as a result of the announcement and consummation
of the Business Combination; (9) the Company’s ability to remain compliant with the covenants of its existing debt, including any
convertible or bridge financing notes; (10) HoldCo’s ability to remain compliant with the covenants of, and other obligations under,
the senior secured convertible notes that will be issued in connection with the closing of the Business Combination; (11) the ability
to recognize the anticipated benefits of the Business Combination, which may be affected by, among other things, competition, the ability
of HoldCo to grow and manage growth profitably, maintain relationships with customers and suppliers and retain its management and key
employees; (12) costs related to the Business Combination; (13) risks associated with changes in applicable laws or regulations and the
Company’s or HoldCo’s business operations and any operations in a regulated industry; (14) the possibility that the Company
or HoldCo may be adversely affected by other economic, business, and/or competitive factors; (15) the Company’s or HoldCo’s
use of proceeds, post-Business Combination fully diluted equity value or fully diluted enterprise value, expected pro forma cash, expected
cash runway or funding gap, estimates of expenses and profitability; and (16) the other risks and uncertainties set forth in the sections
entitled “Risk Factors” and “Cautionary Note Regarding Forward-Looking Statements” in CBRG’s Annual Report
on Form 10-K for the year ended December 31, 2023, its Quarterly Reports on Form 10-Q, and other documents filed, or to be filed, with
the SEC by CBRG or HoldCo. There may be additional risks that CBRG, the Company or HoldCo do not presently know or that CBRG, the Company
or HoldCo currently believe are immaterial that could also cause actual results to differ from those contained in the forward-looking
statements. Actual events and circumstances are difficult or impossible to predict and may materially differ from assumptions. Many actual
events and circumstances are beyond the control of CBRG, the Company and HoldCo.
Nothing in this Current Report
should be regarded as a representation or warranty by any person that the forward-looking statements set forth herein will be achieved
or that any of the contemplated results of such forward-looking statements will be achieved, in any specified time frame, or at all. You
should not place undue reliance on forward-looking statements, which speak only as of the date they are made in this Current Report. Subsequent
events and developments may cause those views to change. Neither CBRG, the Company nor HoldCo undertakes any duty to update these forward-looking
statements.
Additional Information
In connection with the Business
Combination, HoldCo intends to file with the SEC a Registration Statement on Form S-4 containing a preliminary proxy statement of CBRG
and a preliminary prospectus of HoldCo, and after the Registration Statement is declared effective, CBRG expects to mail a definitive
proxy statement/prospectus related to the Business Combination to its shareholders. The proxy statement/prospectus will contain important
information about the Business Combination and the other matters to be voted upon at CBRG’s shareholder meeting to be held to approve
the Business Combination. CBRG and HoldCo may also file other documents with the SEC regarding the Business Combination. This Current
Report does not contain all the information that should be considered concerning the Business Combination and is not intended to form
the basis of any investment decision or any other decision in respect of the Business Combination. Before making any voting or other investment
decisions, shareholders of CBRG and other interested persons are advised to read, when available, the preliminary proxy statement/prospectus
and any amendments thereto, the definitive proxy statement/prospectus and other documents filed in connection with the Business Combination,
as these materials will contain important information about CBRG, the Company and the Business Combination. After the Registration Statement
becomes effective, the definitive proxy statement/prospectus and other relevant materials for the Business Combination will be mailed
to shareholders of CBRG as of a record date to be established for voting on the Business Combination. Shareholders will also be able to
obtain copies of the definitive proxy statement/prospectus and other documents filed with the SEC, without charge, once available, at
the SEC’s website at www.sec.gov, or by directing a request to: Chain Bridge I, 8 The Green #17538, Dover, DE, Attention: Chief
Executive Officer.
INVESTMENT IN ANY SECURITIES DESCRIBED HEREIN
HAS NOT BEEN APPROVED OR DISAPPROVED BY THE SEC OR ANY OTHER REGULATORY AUTHORITY NOR HAS ANY AUTHORITY PASSED UPON OR ENDORSED THE MERITS
OF THE OFFERING OR THE ACCURACY OR ADEQUACY OF THE INFORMATION CONTAINED HEREIN. ANY REPRESENTATION TO THE CONTRARY IS A CRIMINAL OFFENSE.
Participants in the Solicitation
CBRG and its respective directors and executive officers may be deemed
to be participants in the solicitation of proxies from CBRG’s shareholders with respect to the Business Combination. A list of the
names of CBRG’s directors and executive officers and a description of their interests in CBRG is contained in CBRG’s Annual
Report on Form 10-K, which was filed with the SEC and is available free of charge at the SEC’s web site at www.sec.gov, or by directing
a request to Chain Bridge I, 8 The Green #17538, Dover, DE, Attention: Chief Executive Officer. Additional information regarding the interests
of such participants will be contained in the proxy statement/prospectus for the Business Combination when available. Investors, security
holders and other interested persons of CBRG, the Company and HoldCo are urged to carefully read in their entirety the proxy statement/prospectus
and other relevant documents that will be filed with the SEC, when they become available, because they will contain important information
about the Business Combination. Also see above under the heading “Additional Information.”
The Company and HoldCo, and
its directors and executive officers may also be deemed to be participants in the solicitation of proxies from the shareholders of CBRG
in connection with the Business Combination. A list of the names of such directors and executive officers and information regarding their
interests in the Business Combination will be included in the proxy statement/prospectus for the Business Combination when available.
No Offer and Non-Solicitation
This Current Report does not
constitute (i) a solicitation of a proxy, consent or authorization with respect to any securities or in respect of the Business Combination
or (ii) an offer to sell, a solicitation of an offer to buy, or a recommendation to purchase any securities of CBRG, the Company or HoldCo,
nor shall there be any sale of any such securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful
prior to registration or qualification under the securities laws of such state or jurisdiction. No offer of securities shall be made except
by means of a prospectus meeting the requirements of Section 10 of the Securities Act, or an exemption therefrom.
| Item 9.01. |
Financial Statements and Exhibits. |
SIGNATURE
Pursuant to the requirements
of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto
duly authorized.
| Dated: July 29, 2024 |
|
| |
|
| |
Chain Bridge I |
| |
|
| |
By: |
/s/ Andrew Cohen |
| |
Name: |
Andrew Cohen |
| |
Title: |
Chief Executive Officer |
Exhibit 99.1
July 29, 2024 CONFIDENTIAL - DO NOT DISTRIBUTE 1
DISCLAIMERS Important Information for Investors This investor presentation (this “Presentation”) (references to which shall be deemed to include any information which has be en or may be supplied in writing or orally in connection herewith or in connection with any further enquiries) relates to a proposed business combination (the “Transact ion ”) between Chain Bridge I (“CBRG”) and Phytanix Bio (together with its subsidiaries and affiliates, “Phytanix”). This Presentation does not contain all of the inf ormation that should be considered with respect to the proposed Transaction. This Presentation is for informational purposes only and is not intended to form any bas is of any investment decision or any other decision in respect of the proposed Transaction. You should consult your own counsel and tax and financial advisors as to leg al and related matters concerning the matters described herein. Industry and Market Data The views and statements provided in this Presentation are based on information derived from Phytanix’s internal estimates and research, studies, publications, surveys and other information provided by third parties and also from publicly available sources. In this Presentation, Phyta nix and CBRG rely on, and refer to, publicly available information and statistics regarding market participants in the sector in which Phytanix competes and other industr y d ata. Any comparison of Phytanix to any other entity assumes the reliability of the information available to Phytanix. Neither Phytanix nor CBRG has independently ve rif ied the accuracy or completeness of these sources. Cautionary Language Regarding Forward Looking Statements This Presentation includes “forward - looking statements.” Forward - looking statements may be identified by the use of words such a s “estimate,” “plan,” “goal,” “project,” “forecast,” “intend,” “will,” “expect,” “anticipate,” “believe,” “seek,” “target” or other similar expressions that predict o r i ndicate future events or trends or that are not statements of historical matters. These forward - looking statements include, but are not limited to, statements regarding Phytani x’ and CBRG’s expectations, hopes, beliefs, intentions or strategies regarding the future including, without limitation, statements regarding: plans for preclin ica l studies, clinical trials and research and development programs; size of anticipated target markets; the anticipated timing of the results from those studies and trials ; e xpectations regarding regulatory approvals; Phytanix’ and CBRG’s expectations with respect to future performance and anticipated financial impacts of the Tran sac tion; the satisfaction of the closing conditions to the Transaction; and the timing of the completion of the Transaction. Forward - looking statements are based on curr ent expectations and assumptions that, while considered reasonable by Phytanix and its management, and CBRG and its management, as the case may be, are inhere ntl y uncertain. These statements are based on various assumptions, whether or not identified herein, and on the current expectations of Phytanix’ and CBRG’s m ana gement and are not predictions of actual performance. These forward - looking statements are provided for illustrative purposes only and are not intended to serve a s, and must not be relied on by any investor as, a guarantee, an assurance, a prediction or a definitive statement of fact or probability. Actual events and circ ums tances are difficult or impossible to predict and will differ from assumptions. Many actual events and circumstances are beyond the control of Phytanix and CBRG . CONFIDENTIAL - DO NOT DISTRIBUTE 2
DISCLAIMERS These forward - looking statements are subject to a number of risks and uncertainties, including ( i ) changes in domestic and foreign business, market, financial, political and legal conditions; (ii) the ability of the partie s t o successfully or timely consummate the Transaction, including the risk that any required regulatory approvals are not obtained , a re delayed or are subject to unanticipated conditions that could adversely affect the combined company or the expected benefits of the Transaction or that the approval of the shareholders of CBRG is not obtained; (iii) f ail ure to realize the anticipated benefits of the Transaction; (iv) risks relating to the uncertainty of projected performance with respect to Phytanix; (v) future global, regional or local economic and market conditions; (vi) the developme nt, effects and enforcement of laws and regulations; (vii) Phytanix’s ability to manage future growth; (viii) changes in the market for Phytanix’s products and services; (ix) the amount of redemption requests made by CBRG’s public stockholders; (x) the outcome of any pote nt ial litigation, government and regulatory proceedings, investigations and inquiries that may be instituted against CBRG, Phytanix, the combined company or others following the anno unc ement of the Transaction and any definitive agreements with respect thereto; (xi) the occurrence of any event, change or other circumstance that could give rise to the termination of the Business Combination Agreement with re spe ct to the Transaction or the inability of CBRG or Phytanix to satisfy the conditions to closing the Transaction; (xii) changes to the proposed structure of the Transaction that may be required or appropriate as a result of ap pli cable laws or regulations or as a condition to obtaining regulatory approval of the Transaction; (xiii) the ability to meet stock exchange listing standards following the consummation of the Transaction; (xiv) the risk that the pende ncy of the Transaction or time required to consummate the Transaction disrupts current plans and operations of Phytanix; (xv) the evolution of the market in which Phytanix operates; (xvi) the ability of Phytanix to commerc ial ize product candidates and achieve market acceptance of such product candidates; (xvii) the ability of Phytanix to defend its intellectual property; (xviii) the ability of Phytanix to satisfy regulatory requirements; and (xix) t hos e factors discussed in CBRG’s Annual Report on Form 10 - K filed with the U.S. Securities and Exchange Commission (the “SEC”) on March 29, 2023 under the heading “Risk Factors,” and other documents of CBRG and Phytanix filed, or to be filed, with the SEC. If any of these risks materialize or CBRG’s or Phytanix’ assumptions prove incorrect, actual results could differ materially from the results implied by these forward - looking statements. There may be add itional risks that neither CBRG nor Phytanix presently know or that CBRG and Phytanix currently believe are immaterial that could also cause actual results to differ from those contained in the forward - looking statements. In additio n, forward - looking statements reflect CBRG’s and Phytanix’ expectations, plans or forecasts of future events and views as of the date of this Presentation. CBRG and Phytanix anticipate that subsequent events and developments wi ll cause CBRG’s and Phytanix’ assessments to change. However, while CBRG and Phytanix may elect to update these forward - looking statements at some point in the future, CBRG and Phytanix specifically disclaim any obligation t o do so except as required by law. These forward - looking statements should not be relied upon as representing CBRG’s and Phytanix’ assessments as of any date subsequent to the date of this Presentation. Accordingly, undue rel iance should not be placed upon the forward - looking statements. No Offer or Solicitation T his Presentation does not constitute an offer, or a solicitation of an offer, to buy or sell any securities, investment or ot her specific product, or a solicitation of any vote or approval, nor shall there be any sale of securities, investment or other specific product in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to re gistration or qualification under the securities laws of any such jurisdiction. Any securities to be offered in any transaction contemplated hereby have not been approved or disapproved by the SEC, any state securities commission or othe r U nited States or foreign regulatory authority, and will be offered and sold solely in reliance on an exemption from the registration requirements provided by the Securities Act and rules and regulations promulgated thereunder (in cluding Regulation D or Regulation S under the Securities Act). This document does not constitute, or form a part of, an offer to sell or the solicitation of an offer to buy in any state or other jurisdiction to any person to w hom it is unlawful to make such offer or solicitation. Consequently, this Presentation does not contain all the information which would be required to be contained in such a prospectus or disclosure document such as, for example, details of the assets and liabilities, financial position, profits and losses and prospects of any of the entities referred to in this Presentation. The material provided in this Presentation is provided for the information of recipients an d d oes not constitute an invitation or inducement to such persons to enter any investment activity relating to those entities. Phytanix and CBRG have not considered the objectives, financial position or needs of any recipient. The recip ien t should obtain and rely upon his or her own professional advice from their tax, legal, accounting, financial and other professional advisors in respect of the recipient’s objectives, financial position or needs before making an y investment decision based on information contained in this Presentation. Neither this Presentation nor any of its contents may be reproduced or used for any other purpose without the prior written c ons ent of Phytanix and CBRG. In accepting this Presentation, the recipient agrees that it is provided solely for its use in connection with providing background information on Phytanix and considering the Transaction and that it is no t t o be used for any other purpose. Should a security described in this Presentation be denominated in a currency other than the recipient’s home currency, a change in exchange rates may adversely affect the price of, value of, or in come derived from the security. Neither this Presentation nor any of its contents is represented to comply with nor is to be construed to comply with any of the legal requirements in any jurisdiction in respect of an offer to bu y or sell or a solicitation of an offer to buy or sell securities. CONFIDENTIAL - DO NOT DISTRIBUTE 3
DISCLAIMERS Participants in the Solicitation CBRG, Phytanix and their respective directors and executive officers may be deemed under SEC rules to be participants in the sol icitation of proxies of CBRG’s stockholders in connection with the Transaction. Investors and security holders may obtain more detailed information regardin g t he names and interests of CBRG’s directors and officers in the Transaction in CBRG’s filings with the SEC, including CBRG’s Annual Report. Information regardi ng the persons who may, under SEC rules, be deemed participants in the solicitation of proxies of CBRG’s stockholders in connection with the Transaction will be set f ort h in the proxy statement/prospectus contained in the registration statement on Form S - 4 for the Transaction. Additional Information and Where to Find It Phytanix intends to file with the SEC a registration statement on Form S - 4 that will include a preliminary proxy statement/prosp ectus to be distributed to stockholders of CBRG in connection with CBRG’s solicitation of proxies for the vote by its stockholders with respect to the Transaction. A fte r the registration statement has been filed and declared effective by the SEC, CBRG will mail the definitive proxy statement/prospectus to all CBRG stockholders as of a rec ord date to be established for voting on the Transaction and other matters as may be described in the registration statement. CBRG and Phytanix also will file other d ocu ments regarding the Transaction with the SEC. Before making any voting decision, investors and security holders of CBRG are urged to carefully read the entire reg ist ration statement, the proxy statement/prospectus and all other relevant documents filed or that will be filed with the SEC, as well as any amendments or sup plements to these documents, in connection with the Transaction as they become available because they will contain important information about the proposed T ran saction. Investors and security holders will be able to obtain free copies of the registration statement, proxy statement/prospectus and all other relevant d ocu ments filed or that will be filed with the SEC by CBRG or Phytanix through the website maintained by the SEC at www.sec.gov . In addition, the documents filed by CBRG may be obtained free of charge by written request to CBRG at 8 the Green, #17538, Dover Delaware, Attention: CEO. CONFIDENTIAL - DO NOT DISTRIBUTE 4
CANNABINOID & CANNABIS - BASED PHARMACEUTICALS: Market Opportunity CONFIDENTIAL - DO NOT DISTRIBUTE 5 • The development of cannabinoid medicines offers the potential for high return on investment • GW Pharma acquired by Jazz Pharmaceuticals for US $7.2 Billion 1 • Epidiolex (DS, LGS & TSC indication – orphan epilepsy indications • Sativex (not approved in the USA; approved in Europe) • Cannabinoids ARE approvable as medicines by FDA & Other International Regulators • Marinol ® , Nabilone ® , Epidiolex ® , Sativex ® ; Syndros ® • Cannabinoid Market Size is potentially very large 1) Pharmaceuticals (Human & Veterinary) • The global cannabis pharmaceuticals market size was estimated at $1.69 billion USD in 2023 and is projected to grow at a compound annual growth rate (CAGR) of 32.6% from 2024 to 2030. 2 2) Cosmetic ingredients • Ingredients may be sold with appropriate approval • Exploitation of the sector comes down to: • Regulatory approval • Cost of Goods • IP protection 1. https://investor.jazzpharma.com/news - releases/news - release - details/jazz - pharmaceuticals - completes - acquisition - gw - pharmaceuticals#:~:text=DUBLIN%20%2C%20May%205%2C%202021%20%2F,of%20cannabinoid%2Dbased%20prescription%20medicines. 2. https://www.grandviewresearch.com/industry - analysis/cannabis - pharmaceuticals - market
CONFIDENTIAL - DO NOT DISTRIBUTE 6 SCIENTIFIC TEAM CONFIDENTIAL - DO NOT DISTRIBUTE Colin Stott - Chief Operating Officer • Medicinal & Pharmaceutical Chemist / Preclinical & Clinical Development Specialist • 19 years with GW Pharma as R & D Operations Director (17 years) and latterly Scientific Affairs Director (International Divis ion , 2 years) • Intimately involved in the invention and development of both Sativex® (THC/CBD) and Epidiolex® (CBD) • Unrivalled knowledge of how to develop high value cannabinoid medicines Dominic Schiller – Chief IP Counsel • Dominic is a qualified European Patent Attorney • 19 years as external IP counsel to GW Pharma • Provided strategic direction, created and managed GW Pharma's IP portfolio • Big Pharma work with GSK, Compass Pathways and advisor to several investment funds Dr. Tamás Bíró – Scientific Advisor • Dr. Tamás Bíró is a world expert in cannabinoids and the skin • He is a co - author on GW Pharma’s dermatology patents with Colin Stott and Dr. Vincenzo di Marzo • He is the former Professor and Chair of the Department of Immunology at the University of Debrecen in Hungary and former Head of the DE - MTA Lendület Cellular Physiology Group of the Hungarian Academy of Sciences located at the Department of Physiology at University of Debrecen. • Former Director of Applied Resaearch at Phytecs Inc. Guy Webber – Preclinical Development Director • Vastly experienced Drug Metabolism and Pharmacokinetic (DMPK) scientist, who has worked in drug metabolism for over 25 years in both contract research and with pharmaceutical companies. • He is an expert in Absorption, Distribution, Metabolism and Excretion (ADME) and the potential for Drug - Drug Interactions (DDIs) of pharmaceutical medicines, particularly with regard to cannabinoid medicines. • Former ADME Projects Manager at GW Pharmaceuticals (now Jazz Pharmaceuticals), and has worked in the area of cannabinoid medicin es for more than 15 years, and, as a contractor, was closely involved in the ADME evaluation of both Sativex® and Epidiolex®.
PHYTANIX’S THERAPEUTIC AREAS OF FOCUS: CONFIDENTIAL - DO NOT DISTRIBUTE INDICATION 1 TREATMENT OF BLADDER PAIN SYNDROME (PAIN & URINARY SYMPTOMS) INDICATION 2 DEVELOPMENT OF A “SIMPLIFIED”CANNABIS EXTRACT (akin to SATIVEX®) DEVELOP AS PER FDA & EMA GUIDANCE (akin to SATIVEX®) TREATMENT OF TREATMENT - RESISTANT FOCAL SEIZURES IN ADULTS (SEIZURES) DEVELOPMENT OF A CHEMICALLY SYNTHESIZED STILBENOID *NEW CHEMICAL ENTITY (with potential for 20 year patent life) DEVELOP AS PER FDA & EMA GUIDANCE (akin to EPIDIOLEX®) 7
BLADDER PAIN SYNDROME (BPS) INDICATION: Estimated Project Specific Costs Through Development Lifecycle Bladder Pain Syndrome (BPS) Indication Amended from: Valuing drugs and biotech companies (baybridgebio.com) Project Specific Direct Costs to Start of Phase 1 $7.1M USD; 15 Months Project Specific Direct Costs to Start of Phase 2 $9.0M USD; 21 Months Project Specific Direct Costs to Start of Phase 3 $16.8M USD; 36+ Months Assumptions: 1) Only 1 Ph 1 study required to progress to Ph2 – others to be conducted in parallel with Ph 2 & Ph 3 2) Assume only 1 Ph 2 study required before progression to Ph 3 3) Assume Ph 3 will be conducted with Licensing Partner Major Inflexion Point 1 Major Inflexion Point 2 Major Inflexion Point 3 Indication Value at LAUNCH (US $ Billions) PBS $4.123 CONFIDENTIAL - DO NOT DISTRIBUTE 8
RATIONALE FOR SELECTION OF BPS INDICATION: Commercial Rationale CONFIDENTIAL - DO NOT DISTRIBUTE 9 1) Large potential market • 3 to 8 million women in the United States may have IC - That is about 3 to 6% of ALL WOMEN in the US 1 • 1 to 4 million men may have IC too 1 2) There are very few FDA approved treatments for Bladder Pain Syndrome (BPS) / Interstitial cystitis (IC) • The last oral medication was ELMIRON® in 1996 2 ; • before that it was RIMSO - 50 ® (1978) 3 3) ELMIRON® Price • Elmiron still sells for $11.99 USD per 100mg capsule 4 • The recommended dose of ELMIRON® is 300 mg/day taken as one 100 mg capsule orally three times daily 5 • Annual cost >$13,000 per patient per year. 4 4) There remains a high unmet medical need • ELMIRON® causes macular issues (Vision dimming, Difficulty reading, Difficulty adjusting to low light) 5 • There are now ELMIRON® lawsuits emerging across the USA 6 5) Cannabinoid clinical trials (with Sativex®) have shown benefit in: • Randomised, controlled clinical trials of neuropathic pain 7, 8, 9 • Randomised, controlled clinical trials of bladder dysfunction 10 1. Interstitial Cystitis Association Website: [https://www.ichelp.org/understanding - ic/learn - about - ic/who - gets - ic/ ) 2. FDA Website: https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=1784 3. https://onlinelibrary.wiley.com/doi/epdf/10.1111/iju.14505 4. https://www.drugs.com/price - guide/elmiron 5. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020193s014lbl.pdf 6. https://www.lawsuit - information - center.com/elmiron - lawsuit - update.html 7. Rog et al. 2005 8. Nurmikko et al. 2007 9. Berman et al. 2004 10. Kavia et al. 2010
RATIONALE FOR SELECTION OF BPS INDICATION: Preclinical Rationale (1) • Cannabinoid receptors are found in the bladder 1 • Cannabinoid receptor expression in the bladder is altered in bladder overactivity 2 • CB1 Knockout mice have a higher urinary frequency and more spontaneous activity than normal (Wild Type (WT)) mice 3 • In vitro, CBD Botanical Extract (containing approx. 4% THC) reduced bladder contractility in rat and human tissue 4 • In vitro, a number of phytocannabinoids (CBD, CBDV, CBG, THCV but not CBC) reduced bladder contractility in mouse tissue 5 CONFIDENTIAL - DO NOT DISTRIBUTE 10 1. Tyagi et al. 2009. Differential expression of functional cannabinoid receptors in human bladder detrusor and urothelium. J Urol. 2009 Apr;181(4):1932 - 8. 2. Bakali , E., McDonald, J., Elliott, R.A. et al. 2016. Cannabinoid receptor expression in the bladder is altered in detrusor overactivi ty. Int Urogynecol J 27, 129 – 139 (2016). 3. Fullhase et al. 2013. Bladder function in a cannabinoid receptor type 1 knockout mouse. BJU International, 113(1), 144 - 151. https://doi.org/10.1111/bju.12350 4. Capasso et al. 2011. Inhibitory Effect of Standardized Cannabis sativa Extract and Its Ingredient Cannabidiol on Rat and Human Bladder Contractility. Urology 77(4):1006.e9 - 1006.e15 5. Pagano et al. 2015. Effect of Non - psychotropic Plant - derived Cannabinoids on Bladder Contractility: Focus on Cannabigerol . Nat Prod Commun . Jun;10(6):1009 - 1012.
RATIONALE FOR SELECTION OF BPS INDICATION: Preclinical Rationale (2) • In vivo a CB1 & CB2 receptor agonist CP55,940 increased the micturition (urinary) interval by 46% and threshold pressure by 124% 1 • In vivo, a non - selective cannabinoid agonist significantly reduced the afferent nerve activity in mice with Cyclophosphamide (CYP) - induced inflamed bladders at bladder pressures above 20 mmHg 2 • In vivo, administration of a non - selective cannabinoid receptor agonist (10 mg/kg Ajulemic acid) significantly suppressed CYP - induced urinary frequency, as evidenced by the increase in the Inter - contraction Interval 3 • CB2 agonist (JWH - 133) activated CB2 receptors and decreased severity of CYP - induced cystitis and reduced bladder inflammation in mice 4 CONFIDENTIAL - DO NOT DISTRIBUTE 11 1. Gratske et al. 2009. Distribution and function of cannabinoid receptors 1 and 2 in the rat, monkey and human bladder. J Urol. 2009 A pr ;181(4):1939 - 48. doi : 10.1016/j.juro.2008.11.079. Epub 2009 Feb 23. 2. Walczak & Cervero 2011. Local activation of cannabinoid CB1 receptors in the urinary bladder reduces the inflammation - induce d sensitization of bladder afferents. Mol Pain. 2011 May 9;7:31. doi : 10.1186/1744 - 8069 - 7 - 31 3. Hiragata et al. 2007. Effects of IP - 751, ajulemic acid on bladder overactivity induced by bladder irritation in rats. Urology. 2007 Jul;70(1):202 - 8. 4. Liu et al. 2020. Cannabinoid receptor 2 activation decreases severity of cyclophosphamide - induced cystitis via regulating au tophagy. Neurourol Urodyn . 2020 Jan;39(1):158 - 169 .
RATIONALE FOR SELECTION OF BPS INDICATION: Clinical Rationale Randomized Controlled Clinical Trial (RCT) Pain Data CONFIDENTIAL - DO NOT DISTRIBUTE 12
RATIONALE FOR SELECTION OF BPS INDICATION: RCT Pain Data CONFIDENTIAL - DO NOT DISTRIBUTE 13
RATIONALE FOR SELECTION OF BLADDER PAIN SYNDROME INDICATION Clinical Rationale: 1. An open - label study of Sativex and THC Extract demonstrated activity after 8 weeks treatment in MS patients with bladder dysf unction • Patients took extracts containing delta - 9 - tetrahydrocannabinol (THC) and cannabidiol (CBD; 2.5 mg of each per spray) for eight w eeks followed by THC - only (2.5 mg THC per spray) for a further eight weeks, and then into a long - term extension. • 21 patients were recruited and data from 15 were evaluated. Urinary urgency, the number and volume of incontinence episodes, fre quency and nocturia all decreased significantly following treatment (P <0.05, Wilcoxon's signed rank test). However, daily total voided, catheterized and urinary incontinence pad weights also decreased s ign ificantly on both extracts. Patient self - assessment of pain, spasticity and quality of sleep improved significantly (P <0.05, Wilcoxon's signed rank test) with pain improvement continuing up to median of 35 weeks . • Brady et al. 2004. An open - label pilot study of cannabis - based extracts for bladder dysfunction in advanced multiple sclerosis. Mult Scler . 2004; 10: 425 - 433 2. A randomised, double - blind, placebo controlled clinical trial Sativex in 135 MS patients • Sativex produced statistically significant decrease from baseline in a number of urinary parameters • Sativex produced statistically significant decrease from baseline in Total number of voids per 24 hours, Number of daytime vo ids , Number of episodes of nocturia, bladder symptom severity and patient global impression of change (after 8 weeks) • Kavia et al. 2010. Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis. Mult Scler . 2010 Nov;16(11):1349 - 59. 3. A randomised, double - blind, placebo controlled clinical trial (CAMS - LUTS study) of cannabis extract and THC in 630 MS patients • A cannabis extract and THC produced statistically significant decrease from baseline in urge incontinence episode rate (after 15 weeks) • In the CAMS - LUTS study, 630 MS patients received oral administration of cannabis extract, Delta(9) - tetrahydrocannabinol (THC) or matched placebo. • All three groups showed a significant reduction, p<0.01, in adjusted urge incontinence episode rate from baseline to the end of treatment: cannabis extract, 38%; THC, 33%; and placebo, 18%. Both active treatments showed significant effects over placebo (cannabis extract, p=0.005; THC, p=0.039). • Freeman et al. 2006. The effect of cannabis on urge incontinence in patients with multiple sclerosis: a multicentre, randomis ed placebo - controlled trial (CAMS - LUTS). Int Urogynecol J Pelvic Floor Dysfunct . 2006; 17: 636 - 641. 4. Survey of BPS / IC patients by Dr. Mary Lynch and team suggested that cannabis was effective in patients with BPS / IC. • Total of n=97 patients surveyed: n=44 were cannabis users, n=53 were non - users (Single Center study) • Of the 45 patients who responded to the question as to whether cannabis was effective, 37 said it was slightly effective or b ett er (82%): 36% (Slightly Effective); 36% Effective, 11% Very Effective • Of the 48 patients who responded to the “Negative Side Effects” question: 60% said they had none. [27% mild, 6% moderate, 6% sev ere side effects] • Of the 44 patients who responded to the question about any medication changes: 61% reported no change, 27% reported a decreas e i n medication and 18% discontinued medication. No - one reported an increase in medication. CONFIDENTIAL - DO NOT DISTRIBUTE 14
CONFIDENTIAL - DO NOT DISTRIBUTE 15 All but one of the secondary endpoints were statistically in favour of THC: CBD in this study RATIONALE FOR SELECTION OF BPS INDICATION: Randomised, Controlled Trials (RCTs) - Bladder Data SATIVEX has already shown to be effective in an RCT of Bladder Dysfunction ( Kavia et al. 2010)
INTELLECTUAL PROPERTY PROTECTION FOR BPS INDICATION • Dominic Schiller built a robust and effective Intellectual Property position covering Sativex (a cannabis - based medicine made fr om complex cannabis extracts) used to tread spasticity in MS and Epidiolex (a highly purified CBD) used to treat seizures in Dra vet Syndrome (DS), Lennox - Gastaut Syndrome (LGS) and Tuberous Sclerosis Complex (TSC) • At a minimum, a medicine comprising of a new extract would be entitled to regulatory data exclusivity * • 5 years in the USA; 10 years in Europe * Data exclusivity. = Period of time during which an applicant cannot rely on the data in support of another marketing authorisa tion for the purposes of submitting an application, obtaining marketing authorisation or placing the product on the market (i.e.: generics, hybrids, biosimilars) • The same principles apply to the approach we will take for the extract we take into BPS/IC • We expect to create new IP providing an extended period of protection (potentially up to 25 years in Europe using patents and SP C protection (patent extension based on approval). • Example of patented plant extracts obtained include: • WO2004016277 (Sativex): Link to patent WO2004016277 • WO2011032502 ( Reducose – a mulberry extract for pre - diabetes): Link to patent WO2011032502 • Can protect • Extraction methodology (process patent) – here we will look to access to new IP (unpublished from Unified Science) • The extract per se (i.e. the composition of the extract) - (argue inventive step based on simplification) • Formulation patents (e.g. Nano4m and next generation IP for a modified extract) • Medical use patents • Support required (e.g. Efficacy data from an in vivo model of BPS / IC (e.g. CYP - induced IC)) – possibly with comparator drug CONFIDENTIAL - DO NOT DISTRIBUTE 16
CANNABIS BASED MEDICINES CAN SUCCESSFULLY GET THROUGH CLINICAL PHASE 1: Single & Multiple Dose Study CONFIDENTIAL - DO NOT DISTRIBUTE 17
CANNABIS BASED MEDICINES CAN SUCCESSFULLY GET THROUGH CLINICAL PHASE 1: Fed v Fasted Pk Study CONFIDENTIAL - DO NOT DISTRIBUTE 18
TYPICAL PHARMACEUTICAL DEVELOPMENT TIMELINE: Time From Project Start To Regualtory Application For Clinical Phase 1 CONFIDENTIAL - DO NOT DISTRIBUTE 19
POTENTIAL MANUFACTURING PARTNERS FOR PRODUCT DEVELOPMENT BPS / IC Project United Science Holdings (Osceola, Wisconsin) • Capable of producing Botanical Extracts and Ingredients/ High Purity Isolates • Cannabinoids, Terpenes, Flavonoids, Alkaloids, Xanthins • Extraction Equipment (can handle up to 3 Tons/Day Biomass) • Continuous Manufacturing Operations (Wiped Film Distillation) • Chromatography Separations (Up to 100Kg / hour): Cannabinoids, Alkaloids • Formulation & Laboratory Support Epilepsy Project Curia (formerly Albany Molecular Research, Inc. (AMRI), NY) • Well known CDMO – synthesized cannabinoid APIs • Capable of undertaking Custom API Manufacturing • Fermentation • Finished Dosage Forms & Lipid Nanoparticles Purisys (formerly Noramco Inc. (Wilmington, Delaware) • Well known CDMO – synthesized cannabinoid APIs • Specialize in: Process Development, Synthetic Chemistry, Analytical Capabilities, Small Scale Manufacturing, Regulatory Capabilities • Specialize in Controlled Substance API manufacturing • Cannabinoid APIs, Psychedelics & Other Controlled Substances Sterling Pharma Solutions (North Carolina, USA; Wisconsin USA; Various locations, UK) • Full - service API development, scale up and cGMP contract manufacturing services from grams to tonnes • Support for drug discovery process, from initial screening to lead optimisation • Analytical services to support the entire molecule lifecycle • Multidisciplinary approach to early scale - up CONFIDENTIAL - DO NOT DISTRIBUTE 20
POTENTIAL CRO PARTNERS FOR PRECLINICAL / PRODUCT DEVELOPMENT (formerly Covance) – UK, Germany, US, Singapore & China locations • Labcorp did much of the preclinical development for Sativex and all of it for Epidiolex. • Very experienced in the setup, validation and bioanalysis of cannabinoids in plasma samples from preclinical studies UK, Germany & USA locations • Evotec have an integrated platform approach from API availability to Clinical Phase 1 approval UK location • Sequani did much of the early preclinical development for Sativex. Various Locations: UK, USA & China • Pharmaron did all of the ADME / DMPK for Sativex and Epidiolex (UK) Various Locations: UK, USA, Canada, France & Netherlands • Unknown whether Charles River has any experience of developing cannabinoids • GW Pharma did not use Charles River during the Sativex and Epidiolex developments CONFIDENTIAL - DO NOT DISTRIBUTE 21
TREATMENT - RESISTANT FOCAL SEIZURES IN ADULTS ( T RFSA) INDICATION: Estimated Project Specific Costs Through Development Lifecycle Amended from: Valuing drugs and biotech companies (baybridgebio.com) $7.5M USD; 15 Months $9.0M USD; 21 Months $17.2M USD; 36+ Months Assumptions: 1) Only 1 Ph 1 study required to progress to Ph2 – others to be conducted in parallel with Ph 2 & Ph 3 2) Assume only 1 Ph 2 study required before progression to Ph 3 3) Assume Ph 3 will be conducted with Licensing Partner 4) Assume Ph 2 will take at least 18 months Major Inflexion Point 1 Major Inflexion Point 2 Major Inflexion Point 3 Treatment - Resistant Focal Seizures Indication (TRFS) Indication Value at LAUNCH (US $ Billions) TRFSA $2.506 CONFIDENTIAL - DO NOT DISTRIBUTE Project Specific Direct Costs to Start of Phase 1 Project Specific Direct Costs to Start of Phase 2 Project Specific Direct Costs to Start of Phase 3 22
RATIONALE FOR SELECTION OF TRFSA INDICATION: Commercial Rationale: CONFIDENTIAL - DO NOT DISTRIBUTE 23 1) Large potential market • In a systematic review and meta - analysis of the prevalence and incidence of epilepsy: • active generalized epilepsy was found to be the most prevalent (4.33 per 1,000 individuals) 1 , while • active focal seizures accounted for 2.99 per 1,000 individuals 1 2) There is a recent precedent with regard to FDA approved treatments for TRFSA • XCOPRI approved by the FDA in November 2019 2 • ONTOZRY (European Name for XCOPRI) approved by EMA in March 2021 3 3) XCOPRI® Price • XCOPRI® sells for more than $14,000 USD per patient per year in the USA 4 4) There remains a high unmet medical need • EPIDIOLEX® is approved in its current indications (not include TRFSA) at relatively high doses (10 or 20mg/kg/day) 5 • It has a sesame oil base and is a 100mg/mL CBD concentration 5 • Daily adult dose at 20mg/kg/day = approx. 1500mg CBD per day (= 15mL of oily solution ) 5 5) PHYTANIX DEVELOPMENT CANDIDATE EFFECTIVE IN IN VIVO MODEL of SEIZURE: • Similar in vivo model to that used for CBD - To be tested in other models 6 • Potency / Bioavailability likely to be improved by further modification 1. Fiest et al. 2017 Neurology 2017;88:296 – 303 2. https://www.fda.gov/news - events/press - announcements/fda - approves - new - treatment - adults - partial - onset - seizures 3. https://www.ema.europa.eu/en/medicines/human/EPAR/ontozry#:~:text=Ontozry%20received%20a%20marketing%20authorisation,EU%20on% 202 6%20March%202021 . 4. Xcopri Prices , Coupons, Copay & Patient Assistance - Drugs.com 5. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/210365s015lbl.pdf 6. Phytanix Inc. Data on File
RATIONALE FOR SELECTION OF TRFSA INDICATION: Preclinical Rationale: CONFIDENTIAL - DO NOT DISTRIBUTE 24 0 100 200 300 400 500 600 700 Vehicle Diazepam (30mg/kg) Product 1 (200mg/kg) Product 2 (200mg/kg) CBD (100mg/kg) Latency to Tonic Hindlimb Seizure (seconds) Tonic Hindlimb Seizures **** *** **** ****P <0.0001 ***P <0.0006 ns P=0.1578 ns • Product 1 & Product 2 invented by Colin Stott (as Phytotherapeutix Ltd, a UK subsidiary of Phytanix Inc. ) • Patent filed for Products 1 and 2 • Product 1 has “1 st Medical Use” IP • Product 2 is a New Chemical Entity • Similar “next - generation” products in development with view to selecting lead candidate • Phytanix believes that these and similar products will behave like CBD • Possible that such products will have similar wide pharmacology as CBD • Possibility to develop for a range of indications including: • CNS disorders such as epilepsy, psychosis, depression, neurodegenerative disorders etc. • Other disorders: cardioprotection , metabolic disorders etc. Amended from Published Patent Application No.: US63003270 / WO2021198692(A1)
RATIONALE FOR SELECTION OF TRFSA INDICATION: Clinical Rationale (1) CONFIDENTIAL - DO NOT DISTRIBUTE CBD IS EFFECTIVE IN MULTIPLE RANDOMIZED, DOUBLE - BLIND PLACEBO - CONTROLLED CLINICAL STUDIES OF SEZIURE 25
RATIONALE FOR SELECTION OF TRFSA INDICATION: Clinical Rationale (2) CONFIDENTIAL - DO NOT DISTRIBUTE 26
Kochen et al. 2023: CBD as an adjuvant treatment in adults with drug - resistant focal epilepsy • Worsening (increase number of seizures), • Non - responders = (decrease number of seizures between 0 – 50%), • R esponders (decrease number of seizures by 50% or more) CONFIDENTIAL - DO NOT DISTRIBUTE 27 • The initial dose was 250 mg/day. • The median dose, at the end of the trial was 335 mg/day. • The subgroup of the 38 responding patients ended with a mean of 329 mg/day. • 20 patients (53%) completed the trial with a dose of 250 mg/d of CBD • 12 patients (32%) = 375 mg/day • 6 patients (16%) = 500 mg/d. • While patients in the non - responders group had a mean dose of • 350 mg/day • The worsening group ended with 500 mg/day of CBD
Jazz Pharmaceuticals: CBD in Focal Seizures : American Epilepsy Society (AES) 2023 • Effect of CBD (Epidiolex®) in Treatment resistant Focal Seizures • CBD (Epidiolex®) produces a 62% reduction in focal seizures after 144 weeks of treatment (Expanded Access Program) • At least 50% reduction (responder rate) was reported in 51% – 72% of patients for focal seizures at 12 - week visit windows through 144 weeks CONFIDENTIAL - DO NOT DISTRIBUTE 28
Park et al. AES 2023: Long - Term Effectiveness of CBD Against Focal - Onset Seizures in Treatment - Resistant Epilepsies (TRE) CONFIDENTIAL - DO NOT DISTRIBUTE 29
Park et al. AES 2023: Long - Term Effectiveness of CBD Against Focal - Onset Seizures in Treatment - Resistant Epilepsies (TRE) CONFIDENTIAL - DO NOT DISTRIBUTE 30 • CBD (Epidiolex®) produces a 94% reduction in Focal Aware Seizures (FAS) after 144 weeks of treatment (Expanded Access Program) • CBD (Epidiolex®) produces a 78% reduction in Focal Impaired Awareness Seizures (FIAS) after 144 weeks of treatment (Expanded Access Program) • CBD (Epidiolex®) produces a 77% reduction in Focal - to - Bilateral Tonic - Clonic Seizures (FBTCS) after 144 weeks of treatment (Expanded Access Program)
AES = American Epilepsy Society TRE = Treatment - Resistant Epilepsies CONFIDENTIAL - DO NOT DISTRIBUTE 31 Park et al. AES 2023: Long - Term Effectiveness of CBD Against Focal - Onset Seizures in TRE (50%, 75% and 100% Response Rates) 50% Responders 7 5% Responders 10 0% Responders
Park et al. AAN 2024: Long - Term Effectiveness of CBD Against Focal - Onset Seizures in TRE (50%, 75% and 100% Response Rates) ABSTRACT ( https://index.mirasmart.com/AAN2024/SearchResults.php?Author_Institution=&Program_Number=&Topic=&Session_Name=&Author=Park%2C +Yo ng&Title= ) • Long - term Effectiveness of Cannabidiol (CBD) Against Focal - onset Seizures in Treatment - resistant Epilepsies (TRE): Experience fr om the Expanded Access Program (EAP) • Objective : To report the effect of CBD in EAP patients with focal - onset seizures, including focal aware seizures (FAS), focal impaired awareness seizures (FIAS), and focal to bilateral tonic - clonic seizures (FBTCS) . • Background : Four - year EAP results demonstrated that CBD was associated with sustained seizure improvement in TRE . • Design / Methods : Patients received plant - derived highly purified CBD (Epidiolex ® ; 100 mg/mL oral solution) starting at 2 – 10 mg/kg/d and further titrated to a maximum of 25 – 50 mg/kg/d . Percentage change from baseline in median monthly frequency of focal seizures and responder rates (RRs) across 12 - week intervals through 144 treatment weeks were evaluated . • Results : • Of 892 EAP patients , 351 ( 39 % ) experienced focal seizures . Mean (range) age : 15 . 8 (< 1 – 73 . 2 ) years . • Median (range) Anti - Seizure Medications (ASMs) at baseline : 3 ( 0 – 10 ) . Most common ASMs : clobazam ( 43 % ), levetiracetam ( 35 % ) . • Patients withdrew mainly because of lack of efficacy ( 18 % ) or AEs ( 5 % ) . • Median CBD exposure : 684 days (range, 10 – 1793 ) & Median top CBD dose : 25 mg/kg/d (IQR, 24 – 31 ) . • Baseline median (IQR) monthly seizure frequency : 28 ( 4 – 87 ) for FAS, 22 ( 7 – 76 ) for FIAS, and 12 ( 4 – 41 ) for FBTCS . • CBD treatment was associated with median reduction of 67 % – 99 % (FAS), 61 % – 78 % (FIAS), and 50 % – 81 % (FBTCS) . • The FAS Response Rates (RRs) were 61 % – 88 % (≥ 50 % reduction), 45 % – 72 % (≥ 75 % reduction), and 20 % – 46 % ( 100 % reduction) . • The FIAS RRs were 55 % – 69 % , 41 % – 56 % , and 18 % – 29 % , respectively . • The FBTCS RRs were 52 % – 69 % , 41 % – 54 % , and 23 % – 36 % , respectively . • Among patients with any focal seizure, 90 % reported AEs and 38 % serious AEs ; 7 % withdrew due to AEs . Five deaths, not considered treatment - related, occurred in the cohort . Most common AEs : diarrhea ( 40 % ), convulsion ( 24 % ), somnolence ( 21 % ) . Liver - related AEs (> 1 % ) were increased ALT and AST ( 4 % each) and abnormal liver function test ( 3 % ) . • Conclusions : CBD treatment was associated with reduction in focal seizures with an acceptable safety profile . CONFIDENTIAL - DO NOT DISTRIBUTE 32
PHYTANIX INTELLECTUAL PROPERTY (1) Phytanix patent families: • PTX0001 Patent Family • “ Terpenophenolic Compounds And Their Use” • Patent has been Granted • PTX0002 Patent Family • “ Terpenophenolic Scaffolds and a Method for Producing Same” • This patent builds on PTX001 family and covers more than 400 compounds CONFIDENTIAL - DO NOT DISTRIBUTE 33
PHYTANIX INTELLECTUAL PROPERTY (2) Patent Family Status Patent Family Ref Patent Owner Country Filing Date Filing Code Nat/Reg entry Date Nat/Reg entry Number PTX P0001 AUw Phytotherapeutix Ltd* Australia 31 March 2021 PCT/GB2021/050812 28 October 2022 2021248627 PTX P0001 BRw Phytotherapeutix Ltd Brazil 31 March 2021 PCT/GB2021/050812 28 September 2022 BR1120220196164 PTX P0001 CAw Phytotherapeutix Ltd Canada 31 March 2021 PCT/GB2021/050812 27 September 2022 3,177,186 PTX P0001 CNw Phytotherapeutix Ltd China 31 March 2021 PCT/GB2021/050812 28 November 2022 202180038597.7 PTX P0001 EPw Phytotherapeutix Ltd European Patent Office 31 March 2021 PCT/GB2021/050812 24 October 2022 21717177.6 PTX P0001 GBw Phytotherapeutix Ltd United Kingdom 31 March 2021 PCT/GB2021/050812 24 October 2022 2215746.5 PTX P0001 ILw Phytotherapeutix Ltd Israel 31 March 2021 PCT/GB2021/050812 28 September 2022 296861 PTX P0001 INw Phytotherapeutix Ltd India 31 March 2021 PCT/GB2021/050812 28 October 2022 202217061487 PTX P0001 JPw Phytotherapeutix Ltd Japan 31 March 2021 PCT/GB2021/050812 30 September 2022 2022 - 560311 PTX P0001 KRw Phytotherapeutix Ltd Republic of Korea 31 March 2021 PCT/GB2021/050812 28 October 2022 10 - 2022 - 7037909 PTX P0001 MXw Phytotherapeutix Ltd Mexico 31 March 2021 PCT/GB2021/050812 23 September 2022 MX/a/2022/011832 PTX P0001 USw Phytotherapeutix Ltd United States of America 30 September 2022 17/958,083 30 September 2022 17/958,083 PTX P0001 WO Phytotherapeutix Ltd WIPO 31 March 2021 PCT/GB2021/050812 PTX P0001 ZAw Phytotherapeutix Ltd South Africa 31 March 2021 PCT/GB2021/050812 28 October 2022 2022/11785 PTX P0002 GB3 Phytotherapeutix Ltd United Kingdom 30 January 2024 GB2401215.5 CONFIDENTIAL - DO NOT DISTRIBUTE * Phytotherapeutix Ltd is a UK subsidiary of Phytanix Inc. 34
FORMULATION TECHNOLOGY IN - LICENSED BY PHYTANIX : Leucine improves the dissolution rate of a formulation of Ibuprofen • Leucine improves the dissolution rate of a formulation of Ibuprofen • Dissolution rate is a marker of increased oral bioavailability • Leucine increases the flowability of the powder (less sticky!) • Allows it to be spray dried more easily • Leucine allows greater compactability of the powder • Can get more powder into a single capsule • Leucine may improve the stability of the Active Pharmaceutical Ingredient (API) – to be confirmed • This will be particularly helpful for the unstable cannabinoid acids • increases the flowability of the powder (less sticky!) CONFIDENTIAL - DO NOT DISTRIBUTE 35 PHYTANIX WILL UTILISE THIS TECHNOLOGY WITH THE AIM OF INCREASING THE ORAL BIOAVAILABILITY OF ITS DRUG DEVELOPMENT CANDIDATES
PHYTANIX INC. – PROPOSED OPERATING STRUCTURE CONFIDENTIAL - DO NOT DISTRIBUTE 36 COO Colin Stott CMO (TBA) CIPO Dominic Schiller CFO (TBA) CEO Barrett Evans Executive Management Team Senior Management Team Analytical Services Director (In discussions) Regulatory Affairs Director (in discussions) Clinical Operations Director (in discussions) Guy Webber Preclinical Dev. Director (appointed) Quality Director (in discussions) Chief Medical Officer (TBA) Formulation Director (in discussions) Manufacturing Director (TBA) PHYTANIX INC. BOARD BOARD COMPOSITION TO BE AGREED VP, Botanical Cultivation (in discussions) Staff in bold text appointed or close to being appointed, subject to funding *To be appointed VP Translational Research (US) (in discussions) US, VP Discovery Research (in discussions) VP Dermatology (Cosmetics) (in discussions) CSO (TBA)
UNITED STATES HIRES EX - US (UK, & AUSTRALIA) HIRES ALETROLA RECRUITMENT: The Benefit of Experience in t he Cannabinoid Pharma Industry 37 Regulatory Affairs VP / Director Regulatory Affairs (ex - GW Reg Affairs >5 years CB experience) - In discussions Regulatory Affairs Manager (ex - GW Reg Affairs >10 years CB experience) - - in discussions Technical Dept VP / Technical Services Director Analytical Experienced CB Analytical Director (10years +) - In discussions Preclinical VP / Director ADME (>20 yrs ADME CRO experience & ex - GW ADME manager (CB experience)) Quality Assurance (QA) VP / Quality Director (ex - GW Quality – Qualified Person; > 9 years CB experience – in discussions Formulation Development VP / Director Formulation Development Ex - founder of Vectura – in discussions Clinical Development Chief Medical Officer (MD) (TBA) VP Clinical Operations (>15 years CB medicine experience) – in discussions US Preclinical Operations US Clinical Operations US Discovery Research Director (US) (Cannabinoid Research Specialist, 10+ years CB experience; and experienced CB Medical Sales Liaison - - in discussions US VP, Translational Research [Exact Title To Be Agreed] (Cannabinoid clinical research specialist and molecular biologist, 10 years CB experience; Ex - GW Clinical Operations & MSL; Ex - Canopy Director of Research - in discussions IN DISCUSSIONS WITH CANNABINOID MEDICINE EXPERIENCED PROFESSIONALS CONFIDENTIAL - DO NOT DISTRIBUTE Manufacturing Operations Manufacturing Director (US) Experienced Pharmaceutical Manufacturing Director VP / Botanical Research & Cultivation (ex - GW Botanical Research Manager) – in discussions >20 years experience in cannabis cultivation at GW Botanical Cultivation Senior Director, Clin Operations (>15 years CB medicine experience) – in discussions
ANY QUESTIONS ? CONFIDENTIAL - DO NOT DISTRIBUTE 38
July 29, 2024 CONFIDENTIAL - DO NOT DISTRIBUTE 39 APPENDIX
Schedule 1 Status of Cannabis in the USA • Cannabis is currently scheduled as Schedule 1 by the DEA under Federal Law (Controlled Substances Act 1970 & amendments) • Under the law this means that it has “No medical value” • Discussion as to whether the DEA will reschedule cannabis to Schedule 2 or Schedule 3 – yet to happen • The 2018 “Farm Bill” exempted Hemp from this control as long as the THC content was below 0.3%w/w • To date DEA has issued 8 such licences • We have an opportunity to acquire one of these 8 licences CONFIDENTIAL - DO NOT DISTRIBUTE 40
ASSET PURCHASE / IN - LICENSING AGREEMENTS IN PLACE • Phytanix has a number of Licensing / Asset Purchase Agreements in place: • Ferven Asset Purchase Agreement • The terms of this agreement enables Ferven (and thus Alterola) to use a specific micro - organism for genetic engineering for the production of cannabinoids • Nano4M Licensing Agreement • This covers the use of Nano4M nano formulation technology to be applied to Phytanix’s Active Pharmaceutical Ingredients (APIs) • This technology has already been applied to Ibuprofen • It is anticipated that this may increase bioavailability between 4 - 5 fold • Phytanix is currently in discussions with a number of parties with regard to other acquisitions / mergers / in - licensing opportunities which includes: • Extraction and Manufacturing capability • Other patented cannabinoid molecules with improved bioavailability • DEA Schedule 1 Licence CONFIDENTIAL - DO NOT DISTRIBUTE 41
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