InDex Pharmaceuticals has entered into a conditional agreement regarding a reverse merger with Flerie

On May 20, 2024 InDex Pharmaceuticals Holding AB (publ) ("InDex Pharmaceuticals" or the "Company") reported to have entered into a conditional agreement to acquire all shares in Flerie Invest AB (Press release, InDex Pharmaceuticals, MAY 20, 2024, View Source [SID1234643450]). The acquisition is made through an issue in kind of 6,073,952,948 new shares in the Company, following which Flerie Invest AB’s shareholders will initially hold approximately 91.9 per cent of the shares and InDex Pharmaceuticals’ existing shareholders will initially hold approximately 8.1 per cent of the shares in the Company.

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The transaction in brief

InDex Pharmaceuticals has entered into an agreement with the shareholders of Flerie Invest AB ("Flerie") to acquire all shares in Flerie through an issue in kind of 6,073,952,948 new shares in the Company (the "Consideration Shares", and the "Transaction", respectively). Through the Transaction, Flerie will become a wholly-owned subsidiary of InDex Pharmaceuticals and Flerie’s shareholders will initially hold approximately 91.9 per cent of the total number of shares and votes in the Company, prior to the completion of the Capital Raise (as defined below). As a result of the Transaction, the Company will change its name to Flerie AB ("New Flerie").
Flerie is valued at approximately SEK 3,073 million in the Transaction, based on reported net asset value as of 31 March 2024 with a discount of 10 per cent. InDex Pharmaceuticals is valued at approximately SEK 269 million, corresponding to the Company’s estimated cash position after closing costs with a premium of 20 per cent, which entails a subscription price of approximately SEK 0.506 per Consideration Share.
As part of the Transaction and the continued financing of New Flerie, a number of institutional investors, including the Company’s existing shareholders the Fourth Swedish National Pension Fund, HBM Healthcare Investments, Linc AB and SEB Stiftelsen, have undertaken to subscribe for new shares in the Company in a directed share issue (the "Capital Raise"). Through the Capital Raise, the Company will raise in aggregate approximately MSEK 520 before transaction costs.
The Company intends to convene an Extraordinary General Meeting to be held on 10 June 2024, at 8:30 a.m. CEST, to resolve on approval of the Transaction, issue in kind of the Consideration Shares, authorization to issue shares for the Capital Raise, election of new Board members and auditor, and other resolutions that follow from the Transaction (the "Second EGM"). On 6 May 2024 the Company convened an Extraordinary General Meeting to be held on the same day, 10 June 2024 at 8:00 a.m. CEST, to resolve on the amendments to the articles of association that follow from the Transaction (the "First EGM", and together with the Second EGM, the "EGMs").
HBM Healthcare Investments, Linc AB, SEB Stiftelsen and S-E Bankens Utvecklingsstiftelse, who together represent approximately 27.9 per cent of the shares and votes in InDex Pharmaceuticals, have undertaken to vote in favour of the Transaction and related resolutions at the EGMs. Furthermore, the Fourth Swedish National Pension Fund, representing approximately 9.8 per cent of the shares and votes in the Company, has expressed its intention to vote in favour of the Transaction and related resolutions at the EGMs.
The completion of the Transaction is, among other things, conditional upon resolutions at the EGMs and that the Company receives approval for continued listing on Nasdaq First North Growth Market.
Further information about the Transaction, Flerie and New Flerie will be set out in a company description that is expected to be published no later than 27 May 2024.
Background and motive

Following the discontinuation of cobitolimod development and InDex Pharmaceuticals announcing that the Company will not continue the development of any of its other compounds, various options for the Company’s future have been evaluated to maximize shareholder value. This has resulted in the proposed Transaction.

"I am very pleased that the evaluation has resulted in the proposed Transaction, as Flerie came out as the best option. Flerie has a highly regarded Board and management with excellent track record​ and a balanced risk profile. The attractive deal terms include a possibility for share redemption, in addition to being able to trade which ensures that we can offer shareholders optionality", comments Jenny Sundqvist, CEO of InDex Pharmaceuticals.

"This broadening of our shareholder base and becoming listed is a key step in Flerie’s plan to create a new model for life science investing: We continue our long-term, active investment strategy, while offering new shareholders access to and liquidity in difficult-to-assess biotech companies. The Transaction and the Capital Raise allow accelerated development of a risk-diversified portfolio of product development and commercial growth companies spanning obesity, diabetes, heart disease, cancer and autoimmune disorders to pharmaceutical manufacturing services, diagnostics, medical devices and tools", comments Ted Fjällman, CEO of Flerie and intended CEO of New Flerie.

About the Transaction

InDex Pharmaceuticals has today entered into an agreement with the shareholders of Flerie to acquire all shares in Flerie through an issue in kind of 6,073,952,948 new shares (the Consideration Shares) as consideration for the shares in Flerie. The Transaction is a so-called reverse merger whereby Flerie will become a wholly-owned subsidiary of InDex Pharmaceuticals. Flerie’s current shareholders will initially hold approximately 91.9 per cent of the total number of shares and votes in the Company and InDex Pharmaceuticals’ current shareholders will hold approximately 8.1 per cent of the total number of shares and votes in the Company following completion of the Transaction (prior to completion of the Capital Raise).

Flerie is valued at approximately SEK 3,073 million in the Transaction, based on reported net asset value as of 31 March 2024 with a discount of 10 per cent. InDex Pharmaceuticals is valued at approximately SEK 269 million, corresponding to the Company’s estimated cash position after closing costs with a premium of 20 per cent, which entails a subscription price of approximately SEK 0.506 per Consideration Share. The Board of Directors of InDex Pharmaceuticals considers that the valuation applied and the subscription price that the valuation entails is market-based.

Completion of the Transaction is subject to, inter alia, the following conditions, (i) the shareholders of InDex Pharmaceuticals resolving on approval the Transaction and other proposals at the EGMs, (ii) the Company obtaining approval for continued listing on Nasdaq First North Growth Market, and (iii) the Inspectorate of Strategic Products (Sw. Inspektionen för strategiska produkter, ISP) granting necessary approval for the Transaction pursuant to the Screening of Foreign Direct Investments Act (2023:560).

Description of Flerie and New Flerie

Operations

Flerie is an active and global long-term life science investor, focusing predominantly on biotech and pharmaceutical investments. Flerie is based in Stockholm and London managing a portfolio of 32 investments in Europe, Israel, and the US. The focus is on enabling pioneering organisations operating predominantly in the drug development and services space to succeed by providing them with resources and expertise.

Flerie invests in companies across the entire value chain, providing exposure to opportunities across three segments: Product Development, Commercial Growth, and Limited Partnerships. The portfolio includes investments in a wide range of areas, such as immuno-oncology, metabolic diseases and biologics development and manufacturing organisations, which have the potential to make a significant impact on health and wellbeing.

Through its expertise and network, Flerie provides investors with investment flexibility and exposure to difficult-to-access and difficult-to-assess companies within biological pharma, device, product and service innovations. Flerie utilises its broad network of reputable advisers and co-investors for advice on the choice of investment company, investment synergies and due diligence. Flerie´s Pharma network is large and growing and the portfolio companies have initiated collaborations with several well-established international operators.

Flerie was founded in 2011 by Thomas Eldered, who also co-founded and built Recipharm to becoming one of the world’s top five pharmaceutical contract manufacturers.

Flerie’s portfolio

The Product Development segment covers predominantly early-stage biotech and pharma companies which are in the process of advancing products or technologies to clinical proof of concept and towards marketing approval. Product Development companies are characterised by a high valuation uplifting potential and a pathway to success. Flerie may contribute to the development of such companies by encouraging partnering, licensing and expansion of the investor base to provide resources or opportunities. As an active owner, Flerie participates via boards to ensure product plans, platform technology expansion and product roadmaps are optimised. Flerie remains engaged to the appropriate endpoint, which could include the company taking its product to market, entering Commercial Growth. As of 31 March 2024, Fleries invested capital in the segment amounted to approximately SEK 2.2 billion and the fair value amounted to approximately SEK 2.1 billion, divided into 21 companies.

While companies in the Product Development segment are in an early stage of development, those in the Commercial Growth segment have reached a more mature phase and are generating sales. Since the risks of investing in pharmaceutical companies are primarily associated with the early stages of development, investments in Commercial Growth companies generally entail less technical risks, but also relatively lower returns upon a successful development of the company invested in. Flerie’s role in these companies is to assist them with the sales of their products or services to reach profitability, to support expansion through organic growth and through merger & acquisition opportunities. When a Commercial Growth company reaches maturity and Flerie is no longer adding value or it determines that the investment would be better deployed elsewhere, Flerie exits the company. As of 31 March 2024, Fleries invested capital in the segment amounted to approximately SEK 0.7 billion and the fair value amounted to approximately SEK 0.7 billion, divided into eight companies.

Under certain circumstances, Flerie may become a limited partner in an investment fund. Limited Partnerships primarily allow the Company to access the network, opportunities and skills of another investment company or fund and is primarily a way to de-risk the portfolio by diversifying into sectors that are new to Flerie as well as benefitting from the expertise of the specialists there. This way, Limited Partnerships provide advantages for the other two segments and Flerie’s long-term portfolio expansion possibility. As of 31 March 2024, Fleries invested capital in the segment amounted to approximately SEK 72 million and the fair value amounted to approximately SEK 71 million.

Board of directors, management and shareholders etc.

The Board of Directors of New Flerie shall consist of Flerie’s current Board: Thomas Eldered, Cecilia Edström, Anders Ekblom and Jenni Nordborg, with Thomas Eldered as chairman. Following completion of the Transaction, Flerie’s CEO Ted Fjällman will be appointed CEO of New Flerie and Flerie’s CFO and deputy CEO Cecilia Schéele will be appointed CFO and deputy CEO of New Flerie.

Thomas Eldered’s directly and indirectly wholly-owned companies T&M Förvaltning AB and T&M Participation AB (the "Major Shareholders") jointly hold approximately 97 per cent of the shares and votes of Flerie.[1] The remaining shares of Flerie are mainly held by employees and Board members of Flerie. Following the completion of the Transaction, but prior to completion of the Capital Raise, Thomas Eldered will thus become the largest shareholder of New Flerie with an indirect holding of approximately 89.1 per cent of the total number of shares and votes.

The Major Shareholders as well as Flerie’s Board and management will, towards Carnegie Investment Bank AB (publ) and DNB Markets, a part of DNB Bank ASA, Sweden branch (together the "Joint Bookrunners" in connection with the Capital Raise) undertake, with certain exceptions, not to sell or otherwise transfer or dispose of their shares in New Flerie. This lock-up period will last for 360 days from completion of the Transaction for the Major Shareholders and 180 days from completion of the Transaction for Flerie’s Board and management.

The Capital Raise

As part of the Transaction and the continued financing of Flerie, a number of institutional investors, including the Company’s existing shareholders the Fourth Swedish National Pension Fund, HBM Healthcare Investments, Linc AB and SEB Stiftelsen, have undertaken to subscribe for new shares in the Company for an aggregate amount of approximately SEK 520 millions in a directed share issue at a subscription price of approximately SEK 0.506 per share, corresponding to the subscription price per Consideration Share. These commitments are not secured by a bank guarantee, escrow, pledge or similar arrangements.

The purpose of the Capital Raise, and the reasons for the deviation from the shareholders’ preferential right, is to ensure that the Company meets the liquidity requirements for a listing on Nasdaq Stockholm, to ensure continued financing of New Flerie in immediate connection to the implementation of the Transaction, and to diversify and strengthen the shareholder base with institutional investors. Since the subscription price in the Capital Raise corresponds to the subscription price for the Consideration Shares, which is based on a valuation of InDex Pharmaceuticals that has been subject to arm’s-length negotiations with the sellers of Flerie, the Board of InDex Pharmaceuticals considers that the subscription price is market-based.

Through the Capital Raise, the Company will raise in aggregate approximately SEK 520 millions prior to transaction costs. New Flerie intends to use the net proceeds to fulfil its capital commitments, make add-on investments in current portfolio companies to accelerate their development and to improve the liquidity.

The Capital Raise entails a dilution of approximately 13 per cent of the number of shares and votes in New Flerie after completion of the Transaction by increasing the number of shares and votes by 1,025,959,478, from 6,606,640,598 to 7,632,600,076. The share capital increases by SEK 20,519,189.56 to SEK 152,652,001.52.

The Company intends to investigate the conditions to raise additional capital in connection with the share issue to be carried out for the Capital Raise, within the limits of the issue authorisation proposed to be resolved upon by the Second EGM.

New Flerie will undertake, for a period of 360 days from completion of the Transaction, not to, without the Joint Bookrunners’ approval, propose or take measures that entail an increase in the share capital, new share issues and similar measures, with certain exceptions, for example in connection with acquisitions or establishment of incentive programs.

Voluntary share redemption program

In connection with completion of the Transaction, the Company proposes that an annual voluntary share redemption program is established from and including 2025 in order to increase the liquidity of the New Flerie share. Through the redemption program, shareholders are proposed to have the right during an annual conversion period, to occur during the last week of March, to request the conversion of their ordinary shares into a new class of shares, convertible and redeemable shares of series C. Existing shares will constitute ordinary shares. Conversion can take place of up to five (5) per cent of the total number of outstanding shares. If the number of ordinary shares notified for conversion exceeds this limit, distribution shall be made in proportion to the number of ordinary shares that each shareholder has requested for conversion.

As soon as possible following the announcement of the interim report for the first quarter, New Flerie shall redeem all outstanding shares of series C at a redemption amount per share corresponding to the net asset value (NAV) per share as of 31 March. During 2025, certain different time periods will apply for the redemption program.

Further information about the proposed redemption program will be included in the complete proposal for new articles of association, which are proposed to be adopted by the First EGM.

The Major Shareholders and investors in the Capital Raise have undertaken not to exercise the redemption program prior to 2029 and 2026, respectively.

Continued listing on Nasdaq First North and admission to trading on Nasdaq Stockholm

The transaction is conditional upon Nasdaq Stockholm AB approving the Company for continued listing on Nasdaq First North Growth Market. The Company has initiated a process to obtain such approval.

In connection with completion of the Transaction, the Company intends to carry out an uplisting from Nasdaq First North Growth Market to Nasdaq Stockholm. The Company intends to draw up and publish a prospectus in connection with the admission to trading of shares in New Flerie on Nasdaq Stockholm. The prospectus is intended to be registered by the Swedish Financial Supervisory Authority and published on or around 26 June 2024. The first day of trading on Nasdaq Stockholm is planned to take place around 27 June 2024.

The EGMs

The EGMs will be held on 10 June 2024 in order to make the necessary resolutions for completion of the Transaction and the Capital Raise. The notice of the Second EGM will be published through a separate press release and will be available, together with complete proposals for resolutions for the EGMs, on the Company’s website no later than 27 May 2024.

The resolutions relating to the Transaction and the Capital Raise proposed to be made by the EGMs are (i) approval of the Company’s acquisition of Flerie, (ii) the issue in kind of the Consideration Shares to the shareholders of Flerie, (iii) authorisation to issue shares for the Capital Raise, (iv) adoption of new articles of association, including, among other things, change of name to Flerie AB, introduction of convertible and redeemable shares of series C in order to establish the voluntary share redemption program, and the other amendments to the articles of association that follow from the Transaction, (v) election of new Board members and auditor, (vi) reverse share split (1:100) in order to achieve a more appropriate pricing of the New Flerie share, (vii) adoption of principles for appointment of and instructions to the Nomination Committee, and (viii) adoption of guidelines for remuneration to senior executives.

Voting undertakings

HBM Healthcare Investments, Linc AB, SEB Stiftelsen and S-E Bankens Utvecklingsstiftelse, who together represent approximately 27.9 per cent of the shares and votes in InDex Pharmaceuticals, have undertaken to vote in favour of the Transaction and related resolutions at the EGMs. Furthermore, the Fourth Swedish National Pension Fund, representing approximately 9.8 per cent of the shares and votes in the Company, has expressed its intention to vote in favour of the Transaction and related resolutions at the EGMs.

Exemption from mandatory offer

Thomas Eldered will, as described above under the section Description of Flerie and New Flerie – Board of directors, management and shareholders etc., by way of the subscription of Consideration Shares by the Major Shareholders, achieve an indirect shareholding in the Company corresponding to at least three tenths of the voting rights of all shares in the Company after completion of the Transaction. According to the Takeover rules for certain trading platforms, Thomas Eldered would thus be obliged to make a public tender offer for all shares in InDex Pharmaceuticals (so-called mandatory offer obligation) as a result of the Transaction. Thomas Eldered has therefore applied for, and on 16 May 2024 received, an exemption from the Swedish Securities Council regarding the above-mentioned mandatory offer obligation. For further information, see the Swedish Securities Council’s statement 2024:47.

Company description

Further information about the Transaction, Flerie and New Flerie will be presented in a company description that will be published prior to the EGMs.

Indicative timetable for the Transaction

The timetable below is preliminary and subject to change.

21 May 2024 Investor meeting
27 May 2024 Publication of company description
10 June 2024 The EGMs
11June 2024 Completion of the Transaction
14 June 2024 Execution of the Capital Raise
26 June 2024 Expected date for decision by Nasdaq Stockholm AB’s listing committee on whether New Flerie meets the requirements for listing on Nasdaq Stockholm
26 June 2024 Excepted date for announcement of prospectus for admission to trading on Nasdaq Stockholm and last day of trading on Nasdaq First North Growth Market
27 June 2024 Expected first day of trading on Nasdaq Stockholm
Investor meeting

InDex Pharmaceuticals and Flerie invite to a digital investor meeting on 21 May 2024 at 4:00 p.m. CEST in order to inform shareholders about the Transaction and to provide shareholders and stakeholders with the opportunity to ask questions. The meeting will be held by Jenny Sundqvist, CEO, and Johan Giléus, CFO and deputy CEO of InDex Pharmaceuticals, together with Ted Fjällman, CEO of Flerie and intended CEO of New Flerie after completion of the Transaction. The meeting will take place at Redeye’s office at Mäster Samuelsgatan 42 (10th floor) in Stockholm, Sweden. Additionally, the presentation and the Q&A will be webcast.

To register to participate on site at Redeye in Stockholm, please use the following link: View Source
To follow the event via the webcast, please use this link: View Source
Advisors

Redeye AB is financial advisor and Setterwalls Advokatbyrå is legal advisor to InDex Pharmaceuticals in connection with the Transaction. Carnegie Investment Bank AB (publ) is Global Coordinator and Joint Bookrunner and DNB Markets, a part of DNB Bank ASA, Sweden branch is Joint Bookrunner in connection with the Capital Raise and financial advisors to Flerie in connection with the Transaction. KANTER Advokatbyrå KB is legal advisor to Flerie in connection with the Transaction.

For more information:

Jenny Sundqvist, CEO of InDex Pharmaceuticals
Tel: +46 8 122 038 50
E-mail: [email protected]

Johan Giléus, CFO and deputy CEO of InDex Pharmaceuticals
Tel: +46 8 122 038 50
E-mail: [email protected]

Ted Fjällman, CEO of Flerie
E-mail: [email protected]

This information is information that InDex Pharmaceuticals Holding AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation (MAR). The information was submitted for publication through the agency of the CEO on 20 May 2024, at 09.00 p.m. CEST.

Innovent Announces Oral Presentations at ESMO Plenary and ESMO GI Congress on Clinical Data of IBI363 (PD-1/IL-2) and IBI343 (CLDN18.2 ADC)

On May 19, 2024 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported that the company will deliver oral presentations on clinical data of its first-in-class PD-1/IL-2 bispecific antibody fusion protein (R&D code: IBI363) and novel Topoi anti-Claudin18.2 ADC (R&D code: IBI343) at the upcoming medical conferences in June, including ESMO (Free ESMO Whitepaper) Virtual Plenary and ESMO (Free ESMO Whitepaper) Gastrointestinal Cancers Congress (ESMO GI) 2024. Details are as follows (Press release, Innovent Biologics, MAY 19, 2024, View Source [SID1234643430]):

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ESMO Virtual Plenary, June 13-June 14, 2024

Title: First-in-class PD-1/IL-2 bispecific antibody fusion protein IBI363 in patients (pts) with advanced solid tumors: First-in-human phase I study
Presentation Form: Oral
Presentation Time: 13 Jun 2024 18:30-19:30 CEST & 14 June 2024 13:00-14:10 CEST
Presenting Author: Prof. Xueli Bai, The first affiliated hospital, Zhejiang University School of Medicine

ESMO Gastrointestinal Cancers Congress, June 26-June 29, 2024, Munich, Germany

Title: Anti-claudin 18.2 (CLDN18.2) antibody-drug conjugate (ADC) IBI343 in patients (pts) with solid tumors and gastric/gastro-esophageal junction adenocarcinoma (G/GEJ AC): A phase 1 study
Publication Number: 396MO
Presentation Form: Oral
Presentation Time: 29 June 2024 08:45-10:00 CEST
Presenting Author: Jia (Jenny) Liu, St Vincent’s Hospital Sydney

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We will present a robust set of clinical data for our next-generation innovative bispecific antibodies and ADC molecules at multiple conferences in the near term. We observed the preliminary efficacy and safety signals for those innovative candidates, underscoring their potential for further development and clinical value. Innovent leverages our world-class antibody-based platform, differentiated ADC technology and deep scientific understanding to build the new generation innovative pipeline of "IO+ADC". We strive to solve the unmet needs of existing therapies and fill the treatment gap for cancer patients worldwide."

CiMaas and CYTEA BIO are pleased to announce their collaboration on Natural Killer cells

On May 19, 2024 CiMaas reported that it will provide CYTEA BIO with the GMP-grade K562-F012 feeder cells for the expansion of its umbilical cord blood-derived NK cells (Press release, CiMaas, MAY 19, 2024, View Source [SID1234643429]). Conversely, CYTEA BIO will supply CiMaas with Pin antibodies for the pre-arming of CiMaas NK cells to assess the benefit it brings and the opportunity to pursue a longer-term partnership.

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CYTEA BIO is a Swiss/French biotech company dedicated to developing cell therapeutics using its patented Pin platform. This unique approach allows pre-arming Fc-engineered targeting ligands onto genetically unmodified effector cells to orientate and harness a naturally occurring cytotoxicity process. With this platform, an infinite number of products can be envisaged, with ligands and/or effector cells being interchanged. Pre-arming human allogeneic NK cells with Fc-Engineered antibodies (PinTM antibodies) highlighted the power of this strategy, improving the functional and targeted cytotoxicity of the NK cells against various cancer models. CYTEA BIO has initiated a lead development program using pre-armed human allogeneic NK cells with Pin anti-EGFR antibody for the treatment of glioblastoma multiforme.

Ono Receives Approvals of BRAFTOVI® and MEKTOVI® for Expanded Use for Two New Indications in Japan

On May 17, 2024 Ono Pharmaceutical Co., Ltd. reported that it has received supplemental approvals for BRAFTOVI (generic name: encorafenib) Capsule ("BRAFTOVI"), a BRAF inhibitor, and MEKTOVI (generic name: binimetinib) Tablet ("MEKTOVI"), a MEK inhibitor, when used in combination, in Japan for the two new indications of "unresectable thyroid cancer with a BRAF mutation that has progressed following chemotherapy", and "unresectable anaplastic thyroid cancer with a BRAF mutation" (Press release, Ono, MAY 17, 2024, View Source [SID1234646254]).

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 These approvals are based on the results of a Phase 2 study (ONO-7702/7703-03), conducted in Japan in 22 patients with unresectable BRAFV600-mutant thyroid cancer, including 5 patients with anaplastic thyroid cancer. The study met its primary endpoint of objective response rate (ORR) as assessed by the Independent Central Review in the overall patient population, which was 54.5% (12/22 cases, 95% confidence interval: 32.2 – 75.6%) in the combination therapy of BRAFTOVI and MEKTOVI. The safety profile of the combination therapy of BRAFTOVI and MEKTOVI in the study was consistent with those previously reported in the clinical trials of BRAFTOVI and MEKTOVI.

About Phase 2 study (ONO-7702/7703-03)
 The study is a multi-centre, open-label, uncontrolled Phase 2 study (ONO-7702/7703-03), conducted in Japan, evaluating the efficacy and safety of the combination therapy of BRAFTOVI and MEKTOVI in patients with unresectable BRAFV600-mutant thyroid cancer. Patients received the combination therapy with BRAFTOVI 450 mg once daily, and MEKTOVI 45 mg twice daily, until it was determined that treatment could not be given due to disease progression or safety reasons. The primary endpoint of the study was objective response rate (ORR) as assessed by the Independent Central Review. Secondary endpoints include ORR as assessed by physician of each medical institutes, disease control rate (DCR), overall survival (OS) and progression-free survival (PFS).

About Thyroid Cancer
 Thyroid cancer (TC) is a malignant tumor that develops in the thyroid tissue located around the trachea or in front of the neck. Histologically, it is roughly divided into differentiated carcinoma (approximately 97% of TC), undifferentiated carcinoma (1 – 2%), and medullary carcinoma (1 – 2%). In Japan, it is estimated that approximately 18,700 new cases are diagnosed with TC per year with approximately 1,900 deaths per year resulting from the disease in 2023*. BRAF mutation is reported in 37 – 68% of TC patients.

Cancer Statics in Japan, 2024, The Editorial Board of Cancer Statistics, Foundation for Promotion of Cancer Research (FPCR), March 2024

Overview of BRAFTOVI Capsule 50 mg and 75 mg
Product Name BRAFTOVI Capsule 50 mg and 75 mg
Generic name (JAN) Encorafenib
Indication
Unresectable melanoma with a BRAF mutation
Unresectable advanced or recurrent colorectal cancer with a BRAF mutation that has progressed following chemotherapy
Unresectable thyroid cancer with a BRAF mutation that has progressed following chemotherapy
Unresectable anaplastic thyroid cancer with a BRAF mutation
Dosage and administration

In combination with binimetinib, usually, for adults, administer 450 mg of encorafenib orally once a day. According to patients’ condition, the dose should be reduced.

In combination with cetuximab (genetical recombination) or with binimetinib and cetuximab (genetical recombination), usually, for adults, administer 300 mg of encorafenib orally once a day. According to patients’ condition, the dose should be reduced.

Manufacturer/distributor Ono Pharmaceutical Co., Ltd.
Note: Underlined parts show the revised ones due to this approval.

Overview of MEKTOVI Tablet 15 mg
Product Name MEKTOVI Tablet 15 mg
Generic name (JAN) Binimetinib
Indication
Unresectable melanoma with a BRAF mutation
Unresectable advanced or recurrent colorectal cancer with a BRAF mutation that has progressed following chemotherapy
Unresectable thyroid cancer with a BRAF mutation that has progressed following chemotherapy
Unresectable anaplastic thyroid cancer with a BRAF mutation
Dosage and administration

In combination with encorafenib, usually, for adults, administer 45 mg of encorafenib orally twice a day. According to patients’ condition, the dose should be reduced.

In combination with encorafenib and cetuximab (genetical recombination), usually, for adults, administer 45 mg of binimetinib orally twice a day. According to patients’ condition, the dose should be reduced.

Manufacturer/distributor Ono Pharmaceutical Co., Ltd.
Note: Underlined parts show the revised ones due to this approval.

About BRAFTOVI and MEKTOVI
 BRAFTOVI is a small molecule BRAF kinase inhibitor and MEKTOVI is a small molecule MEK inhibitor. BRAF and MEK are important protein kinases in the MAPK signalling pathway (RAS-RAF-MEK-ERK), which regulates several key cellular activities including proliferation, differentiation, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many types of cancers including melanoma, colorectal cancer and thyroid cancer. Both BRAFTOVI and MEKTOVI target key enzymes in this pathway.
 In Japan, Ono received a manufacturing and marketing approval of BRAFTOVI and MEKTOVI for the treatment of unresectable melanoma with a BRAF mutation in combination therapy of the products in January 2019 and launched them in February 2019. Thereafter, Ono received additional approval in November 2020 for the treatment of unresectable advanced or recurrent colorectal cancer with a BRAF mutation that has progressed following chemotherapy, in triplet combination treatment of BRAFTOVI, MEKTOVI and cetuximab, an anti-human EGFR monoclonal antibody, as well as in doublet combination treatment of BRAFTOVI and cetuximab.
 Abroad, Array BioPharma Inc. (a wholly owned subsidiary of Pfizer Inc.) and its collaboration partner, Pierre Fabre, received an approval of BRAFTOVI and MEKTOVI for the treatment of unresectable or metastatic melanoma with BRAFV600E or V600K mutation and launched them in 2018 in the US and EU, respectively. Thereafter, the companies received supplemental approval for the treatment of metastatic colorectal cancer with a BRAFV600E mutation following prior therapy in the US and EU in 2020. Additionally, Pfizer received supplemental approval in the US for the treatment of metastatic non-small cell lung cancer with a BRAFV600E mutation in 2023.

About the Ono Pharmaceutical Co., Ltd. and Pfizer Inc. Collaboration
 In May 2017, Ono entered into the license agreement with Array BioPharma Inc. (became a subsidiary of Pfizer Inc. as of July 30, 2019) regarding BRAFTOVI (encorafenib), a BRAF inhibitor and MEKTOVI (binimetinib), a MEK inhibitor and received rights to develop and commercialize both products in Japan and South Korea.

Autolus Therapeutics Reports First Quarter 2024 Financial Results and Business Updates

On May 17, 2024 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported its operational and financial results for the first quarter ended March 31, 2024 (Press release, Autolus, MAY 17, 2024, View Source [SID1234643422]).

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"We continue to engage with the FDA in the regulatory review process for obecabtagene autoleucel (obe-cel) in adult ALL as we head towards the PDUFA target action date of November 16, 2024, and are driving commercial readiness activities across the Company," said Dr. Christian Itin, Chief Executive Officer of Autolus. "We’re also delighted that our abstracts from the pivotal FELIX Phase 2 trial have been accepted for oral presentations at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) this year and we look forward to sharing further long-term data and additional subset analyses."

"In addition, the first two patients have been enrolled into our dose confirmation trial (CARLYSLE) of obe-cel in Systemic Lupus Erythematosus (SLE) and the study is on track for initial data by end of 2024."

Key obe-cel updates and anticipated milestones:

Obe-cel in relapsed / refractory (r/r) adult B-cell Acute Lymphoblastic Leukemia (ALL) – The FELIX Study
Obe-cel Biologics License Application (BLA) for r/r B-ALL submitted to the FDA in November 2023; PDUFA target action date of November 16, 2024. A marketing authorization application (MAA) to the European Medicines Agency (EMA) was accepted in April 2024. For the UK we are evaluating a filing based on an international recognition procedure.
Pooled analysis of the FELIX Phase 1b/2 study presented at ASH (Free ASH Whitepaper) in December 2023 demonstrated prolonged event free survival and low overall immunotoxicity across all cohorts in r/r B-ALL, and particularly in patients with low leukemic burden at lymphodepletion.
Further long-term data from the FELIX study including additional subset analysis will be presented in oral and poster presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting (ASCO – May 31 – June 4, 2024), and European Hematology Association (EHA) (Free EHA Whitepaper) congress (EHA – June 13 – 16, 2024) respectively.
Obe-cel in B-cell mediated autoimmune diseases
The Phase 1 dose confirmation study (CARLYSLE) in refractory systemic lupus erythematosus (SLE) patients is ongoing. Two patients have been enrolled and Autolus continues to expect initial clinical data in late 2024.
Pipeline clinical trials, in collaboration with University College London (UCL), updates and anticipated milestones:

AUTO8 in Multiple Myeloma – Phase 1 MCARTY Study
AUTO8 is a next-generation product candidate for multiple myeloma, which includes two CARs for the multiple myeloma targets, BCMA and CD19. Initial data from the MCARTY Phase 1 study in multiple myeloma presented at ASH (Free ASH Whitepaper) in December 2023 showed AUTO8 was well tolerated, with responses observed in all patients. Enrollment of the initial cohorts are complete and further updates from the MCARTY study are anticipated in H2 2024.
AUTO6NG in Neuroblastoma – Phase 1 MAGNETO Study
AUTO6NG contains a CAR that targets GD2 alongside additional programming modules to enhance the activity and persistence. A Phase 1 clinical study in children with r/r neuroblastoma was opened for enrollment in the fourth quarter of 2023.
Strategic developments:

In February 2024, BioNTech and Autolus announced a strategic CAR T cell therapy collaboration to advance their pipelines and expand late-stage programs, for $50 million cash upfront and up to $582 million in potential option exercise and milestone payments. Additionally, Autolus sold $200 million of ADSs to BioNTech in a concurrent private placement financing transaction.
In February 2024, Autolus completed an underwritten offering in the United States at a price of $6.00 per ADS, for total gross proceeds of $350 million before underwriting fees and offering expenses.
Operational Updates:

In March 2024, The Nucleus manufacturing facility in Stevenage obtained a Manufacturer’s Importation Authorization (MIA), together with the accompanying GMP certificate. This authorization enables Autolus to manufacture products for global commercial and clinical supply at The Nucleus, effective as of March 18, 2024.
In April 2024, Autolus announced that the European Medicines Agency (EMA) had accepted its Marketing Authorization Application (MAA) for obe-cel for patients with relapsed/refractory (r/r) adult B-cell Acute Lymphoblastic Leukemia (ALL). The MAA submission was based on data from the pivotal Phase 2 FELIX study of obe-cel in adult r/r B-ALL.
In April 2024, Autolus entered into a distribution services agreement with a subsidiary of Cardinal Health to support the ordering and distribution of obe-cel in the United States, following the receipt of regulatory approval.
In April 2024, Autolus announced the appointment of Mike Bonney as Chairman of the Board, and Ravi Rao M.D., as Non-Executive Director. John H. Johnson advised the Board of his decision to step down from his role as Chairman of the Board and Non-Executive Director, effective April 1, 2024.
Scientific Publications:

In January 2024, Autolus announced the publication of a paper in ACS Chemical Biology entitled: ‘Designer small molecule control system based on Minocycline induced disruption of protein-protein interaction’ – Jha et al., ACS Chemical Biology (2024) doi:10.1021/acschembio.3c00521; [Link]
In February 2024, Autolus announced the publication of a paper in Nature Communications entitled: ‘Structure-Guided Engineering of Immunotherapies Targeting TRBC1 and TRBC2 in T Cell Malignancies’ – Ferrari et al., Nat Commun 15, 1583 (2024) doi:10.1038/s41467-024-45854-3; [Link]
In March 2024, Autolus announced the publication of a paper in Blood Cancer Journal entitled: ‘Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry – Horna et al., Blood Cancer J. 14, 34 (2024) doi: 10.1038/s41408-024-01002-0; [Link]
2024 Expected News Flow:

Obe-cel FELIX data update at ASCO (Free ASCO Whitepaper), EHA (Free EHA Whitepaper) & ASH (Free ASH Whitepaper) May, June & Dec 2024
Obe-cel Marketing Authorization Application to MHRA Second half 2024
Obe-cel U.S. FDA PDUFA target action date November 16, 2024
Obe-cel in autoimmune disease – initial data from SLE Phase 1 study Late 2024

Financial Results (Unaudited) for the Quarter Ended March 31, 2024

Cash and cash equivalents at March 31, 2024, totaled $758.5 million, as compared to $239.6 million at December 31, 2023.

Total operating expenses, net for the three months ended March 31, 2024, were $38.8 million, as compared to $39.1 million, for the same period in 2023.

Research and development expenses increased from $27.4 million to $30.7 million for the three months ended March 31, 2024, compared to the same period in 2023. This change was primarily due to increases in operating costs related to the Company’s new commercial manufacturing facility, employee salaries and related costs, clinical trial costs related to obe-cel, and a decrease in our U.K. reimbursable R&D tax credits claimable through the U.K. small and medium-sized entity (SME) scheme. These were partially offset by decreases in professional consulting fees, legal fees, manufacturing costs related to obe-cel clinical supply, information technology infrastructure fees and general office expenses.

General and administrative expenses increased from $9.3 million to $18.2 million for the three months ended March 31, 2024, compared to the same period in 2023. This increase was primarily due to salaries and other employment-related costs driven by an increase in general and administrative headcount supporting the overall growth of the business, primarily relating to pre-commercialization activities.

Net loss was $52.7 million for the three months ended March 31, 2024, compared to $39.8 million for the same period in 2023. The basic and diluted net loss per ordinary share for the three months ended March 31, 2024, totaled $(0.24), compared to a basic and diluted net loss per ordinary share of $(0.23) for 2023.

Autolus estimates that, with its current cash and cash equivalents and proceeds received from the strategic alliance with BioNTech and the private placement and underwritten equity financing, it is well capitalized to drive the full launch and commercialization of obe-cel in r/r adult ALL as well as to advance its pipeline development plans, which includes providing runway to data in the first pivotal study of obe-cel in autoimmune disease.

Financial Results for the Quarter Ended March 31, 2024
Selected Unaudited Condensed Consolidated Balance Sheet Data
(In thousands)

March 31 December 31
2024 2023
Assets
Cash and cash equivalents $ 758,529 $ 239,566
Total current assets $ 804,298 $ 275,302
Total assets $ 901,436 $ 375,381
Liabilities and shareholders’ equity
Total current liabilities $ 43,985 $ 44,737
Total liabilities $ 319,406 $ 263,907
Total shareholders’ equity $ 582,030 $ 111,474

Selected Unaudited Condensed Consolidated Statements of Operations and Comprehensive Loss Data
(In thousands, except share and per share amounts)

Three Months Ended March 31,
2024 2023
License revenues $ 10,091 $ 1,292
Operating expenses:
Research and development (30,671 ) (27,388 )
General and administrative (18,177 ) (9,284 )
Loss on disposal of property and equipment - (3,768 )
Total operating expenses, net (38,757 ) (39,148 )
Total other expenses, net (13,941 ) (677 )
Net loss before income tax (52,698 ) (39,825 )
Income tax benefit 8 14
Net loss (52,690 ) (39,811 )
Other comprehensive income (loss):
Foreign currency exchange translation adjustment 58 5,641
Total comprehensive loss $ (52,632 ) $ (34,170 )

Basic and diluted net loss per ordinary share $ (0.24 ) $ (0.23 )
Weighted-average basic and diluted ordinary shares 222,170,707 173,825,825

Conference Call
Management will host a conference call and webcast at 08:30 am EDT/13:30 pm BST to discuss the Company’s financial results and provide a general business update. Conference call participants should pre-register using this link to receive the dial-in numbers and a personal PIN, which are required to access the conference call.

A simultaneous audio webcast and replay will be accessible on the events section of Autolus’ website.