On April 24, 2023 AB Science S.A. (the "Company" or "AB Science", NYSE Euronext – FR0010557264 – AB), reported the success of its capital increase through the issuance of new ordinary shares with attached warrants, with a waiver of preferential subscription rights, via a private placement for a final amount of 15.0 million euros (the "Capital Increase") (Press release, AB Science, APR 24, 2023, View Source [SID1234630407]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Alain Moussy, Chief Executive Officer of AB Science, states:

« AB Science is satisfied with the success of this capital increase, through which AB Science’s historical shareholders have had the opportunity to renew their confidence in AB Science and to show their support for its new strategy announced on April 21. »
AB Science has decided to focus its development strategy as follows:

– Allocation of current resources primarily to the development of masitinib for the treatment of amyotrophic lateral sclerosis and the development of the microtubule destabilizer agents (MDA) platform, with the clinical development of AB8939 in refractory acute myeloid leukemia and the initiation of regulatory preclinical development of a new oral molecule in the same microtubule class for sarcoma and solid tumors. We want to focus the majority of our clinical resources on the development of rare diseases with masitinib, on the development of the microtubule platform with AB8939 and future molecules of the same family due to the very encouraging first results.

– Acceleration of the process of seeking a license for masitinib in non-rare disease indications, with priority given to progressive forms of multiple sclerosis and Alzheimer’s disease.

This acceleration is possible now that the confirmatory Phase 3 studies have been approved by the FDA in the United States and the major European agencies. To this end, the Company has retained the services of a leading investment bank.

This license search is a priority in the Company’s strategy, given the number of clinical studies already conducted and the maturity of the pipeline, and given the additional investments required to complete the clinical program, up to market authorizations. We want to highlight that the duration of this license search is not predictable and that the realization of a license is dependent on a number of factors and is not guaranteed. However, the milestones reached at this stage are essential factors that contribute to the feasibility of this strategy.

As a result of the focus strategy, AB Science has decided to adapt its organization, which should lead to a significant reduction in costs. This strategic focus reinforces and sustains the existing agreement between certain shareholders of AB Science and Alain Moussy.

Terms of the Capital Increase

The Capital Increase consisted of a private placement pursuant to Articles L. 225-136 of the French Commercial Code and L. 411-2 1° of the French Monetary and Financial Code and has been carried out with a waiver of preferential subscription rights, pursuant to the delegation of authority granted to the Board of Directors under the 20th resolution of the Combined General Shareholders’ Meeting of June 29, 2022. The Capital Increase has taken the form of the issuance of 2,608,686 actions new ordinary shares (the "New Shares") to each of which are attached a share subscription warrant (the "Warrants").
The Capital Increase was made through a cash contribution of approximately EUR 11.5 million and by offsetting existing receivables, i.e. approximately EUR 3.0 million (receivables related to the pre-financing of the research tax credit for the 2020 financial year and maturing in 2023, as well as approximately EUR 500,000 in interest accrued to date on the convertible bonds issued in February 2022).

Two warrants giving the right to subscribe to one ordinary share, all of the 2,608,686 New Shares and all of the 1,304,343 new shares that would be issued upon exercise of the warrants, i.e. a total of 3,913,029 shares in the Company, represent 7.36% of the Company’s current share capital.

The issue price of the New Shares has been set at 5.75 euros (0.01 euro par value and 5.74 euros issue premium) and the exercise price of the Warrants at 8.625 euros, representing a total fundraising of approximately EUR 15.0 million (taking into account the exercise of the warrants, the maximum amount of the Capital Increase could be increased by an amount of 26.3 million euros).

The Warrants may be exercised from January 1st, 2025 to December 31, 2030, will be immediately detached from the New Shares upon their issuance and will not be listed.

The settlement-delivery of the new ordinary shares to be issued in the context of the Capital Increase and their listing on Euronext Paris are expected to occur on April 28, 2023 at the latest. The new shares will bear current dividend rights and will be listed on the regulated market on Euronext Paris under ISIN code: FR0010557264 – AB.

The proceeds of the Capital Increase will provide AB Science with the additional resources necessary to finance its activities over the next twelve months. In particular, the raised funds will be used for the clinical development of masitinib in amyotrophic lateral sclerosis and other orphan indications and for the development of the AB Science microtubule destabilizer agents platform. The Capital Increase will also support the strategy communicated on April 21.

Shareholding structure of the Company after the Capital Increase

After the Capital Increase (excluding the exercise of the Warrants), the share capital of the Company will amount to 558,081.39 euros, and will be composed of 55,808,139 shares with a nominal value of 0.01 euro each (all share classes included). By way of illustration, a shareholder holding 1% of the Company’s share capital (including all categories of shares) prior to the Capital Increase and who did not participate in the Capital Increase will hold 0.95% of the Company’s share capital after the Capital Increase and 0.93% in the event that all the Warrants are exercised. Not for release, publication or distribution, directly or indirectly, in or into the United States of America, Canada, Australia or Japan 3

The table below reflects the shareholding to the best of the Company’s knowledge.

Shareholders Before the Capital Increase After the Capital Increase (before exercise of the warrants) After the Capital Increase and exercise of the warrants Ordinary shares % Ordinary shares % Ordinary shares % A. Moussy 7 058 068 13,27% 7 058 068 12,65% 7 058 068 12,36% AMY SAS 12 273 000 23,07% 12 273 000 21,99% 12 273 000 21,49% Agreement (excluding A. Moussy and AMY SAS) 2 183 696 4,10% 2 673 442 4,79% 2 918 315 5,11% Other investors 31 684 689 59,56% 33 803 629 60,57% 34 863 099 61,04% Total 53 199 453 100,00% 55 808 139 100,00% 57 112 482 100,00%

Information available to the public

The Capital Increase will not be subject to a prospectus approved by the French Financial Market Authority (the "AMF"). AB Science draws the attention of the public to the risk factors relating to the Company and its business described in its annual management reports and press releases, which are available free of charge on the Company’s website (www.ab-science.com).

In addition, the main risks specific to securities are as follows: – The existing shareholders who do not participate in the Capital Increase will see their shareholding in the share capital of AB Science diluted, and this shareholding may also be diluted in the event of exercise of the Warrants, as well as in the event of new securities transactions.

– The volatility and liquidity of AB Science shares could fluctuate significantly. The sale of Company shares may occur on the secondary market, after the Capital Increase, and have a negative impact on the Company share price.

About masitinib

Masitinib is a novel oral tyrosine kinase inhibitor that targets mast cells and macrophages, key immune cells, through inhibition of a limited number of kinases. Due to its unique mode of action, masitinib can be developed in a wide range of diseases, including oncology, inflammatory diseases, and certain central nervous system diseases. In oncology, through its immunotherapy activity, masitinib may have an effect on survival, alone or in combination with chemotherapy. Through its activity on mast cells and microglial cells and therefore its inhibitory effect on the activation of the inflammatory process, masitinib may have an effect on the symptoms associated with certain inflammatory and central nervous system diseases.

About AB8939

AB8939 is a new synthetic microtubule-destabilizing drug. Preclinical data show that AB8939 has broad anticancer activity, with a notable advantage over standard chemotherapies that target microtubules of being able to overcome P-glycoprotein (Pgp) and myeloperoxidase (MPO) mediated drug resistance. Development of drug resistance often restricts the clinical efficacy of microtubule-targeting chemotherapy drugs (for example, taxanes and vinca alkaloids); thus, AB8939 has strong potential to be developed in numerous oncology indications.

On April 24, 2023 – 3B Pharmaceuticals GmbH (3BP), a private German biotechnology company developing targeted radiopharmaceutical drugs and diagnostics for oncology indications, reported that it has entered into an amended and restated licensing agreement with Novartis Innovative Therapies AG (Novartis) for 3BP’s FAP-targeting peptide technology (Press release, 3B Pharmaceuticals, APR 24, 2023, View Source [SID1234630406]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The agreement gives Novartis exclusive worldwide rights to develop and commercialize therapeutic and imaging applications for 3BP’s FAP-targeting peptide technology, including FAP-2286. FAP-2286 targets fibroblast activation protein (FAP), a promising theranostic target with expression across a majority of cancers. FAP-2286 was the first peptide-targeted radioligand therapy (PT-RLT) targeting FAP to enter clinical development together with the respective imaging agent, making it the most advanced radioligand therapy in its class. It is currently being tested in a phase 1 clinical trial (LuMIERE).

Under the terms of the agreement, 3BP receives an initial payment of $40 million as well as up to $425 million in development, regulatory, and commercial milestone payments, in addition to tiered royalties on net sales. 3BP retains certain rights to develop its FAP-targeting imaging technology for diagnostic purposes.

3BP entered into a license and collaboration agreement in 2019 with Clovis Oncology focusing on the development of a peptide-targeted radiotherapy and imaging agent targeting FAP. The new agreement with Novartis encompasses 3BP’s entire FAP-targeting peptide technology and worldwide rights.

"We are grateful to our partner Clovis Oncology for the excellent translation and early clinical development of FAP-2286. We believe the new agreement with Novartis is an ideal partnership for the further clinical development of FAP-2286 for the benefit of patients with many different types of cancer," said Dr. Christiane Smerling, Head of Nuclear Medicine & Imaging at 3BP.

"We have focused for many years on developing a peptide technology platform to create innovative radiopharmaceuticals and this agreement validates the value of 3BP’s platform," added Dr. Ulrich Reineke, Managing Director of 3BP. "This partnership will allow us to continue to expand our core competencies and dedicate resources to the further development of our pipeline."

About FAP-2286

FAP-2286 is a clinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). FAP-2286 consists of two functional elements; a targeting peptide that binds to FAP and a site that can be used to attach radioactive isotopes for imaging and therapeutic use.

On April 23, 2023, IDEAYA Biosciences, Inc. (the "Company") reported interim results from its Phase 2 clinical trial evaluating darovasertib and crizotinib synthetic lethal combination in metastatic uveal melanoma (MUM) patients, its trial design for the Phase 2/3 clinical trial evaluating darovasertib and crizotinib in first-line HLA-A2 negative MUM patients, and interim results for darovasertib as neoadjuvant therapy in primary uveal melanoma (UM), from an ongoing investigator sponsored trial (IST) evaluating darovasertib in (neo)adjuvant uveal melanoma, from compassionate use protocol(s) and from the Company’s Phase 1/2 clinical trial evaluating darovasertib as monotherapy and in combination with crizotinib (Press release, Ideaya Biosciences, APR 23, 2023, View Source [SID1234630428]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Clinical Data Update – Darovasertib and Crizotinib Combination in MUM

The Company observed encouraging clinical activity in the Phase 2 clinical trial evaluating the darovasertib and crizotinib combination in first-line and any-line MUM patients. The reported Phase 2 clinical data are based on 20 evaluable first-line and 63 evaluable any-line patients enrolled as of September 22, 2022 in the darovasertib and crizotinib combination study at the expansion dose of 300 mg twice-a-day darovasertib and 200 mg twice-a-day crizotinib. Reported data are preliminary and based on investigator review from an unlocked database as of the data analyses cutoff date of March 8, 2023. Enrollment in the darovasertib and crizotinib combination expansion dose cohort of the Phase 2 clinical trial is ongoing.

In the 20 evaluable first-line MUM patients in the expansion cohort, the investigator-reviewed data by RECIST 1.1 include:

45% confirmed Overall Response Rate (ORR) in first-line MUM: 9 of 20 evaluable patients had a confirmed partial response (PR)

90% Disease Control Rate (DCR) in first-line MUM: 18 of 20 evaluable patients showed disease control, including 9 confirmed PRs, 1 unconfirmed PR and 8 stable disease

~7 months median progression free survival (PFS) in first-line MUM

In the 63 evaluable any-line MUM patients at the expansion dose, the investigator-reviewed data by RECIST 1.1 include:

30% confirmed ORR in any-line MUM: 19 of 63 evaluable patients had a confirmed PR; the any-line MUM patients were heavily pre-treated, with 63% of patients having received one or more prior lines of treatment and 43% of patients having received two or more prior lines of treatment in the metastatic setting

87% DCR in any-line MUM: 55 of 63 evaluable patients showed disease control, including 19 confirmed PRs, 4 unconfirmed PRs and 32 stable disease

~7 months median PFS in any-line MUM

Observed median PFS increased versus median PFS of ~5 months previously reported in September 2022 with 35 evaluable any-line MUM patients

There were 20 evaluable hepatic-only MUM patients, including first-line and pre-treated patients with only hepatic metastases, for whom the investigator-reviewed data by RECIST 1.1 include:

35% confirmed ORR in hepatic-only MUM: 7 of 20 evaluable patients had a confirmed PR

100% DCR in hepatic-only MUM : 20 of 20 evaluable patients showed disease control, including 7 confirmed PRs, 1 unconfirmed PR and 12 stable disease

~11 months median PFS in hepatic-only MUM

These data demonstrate robust clinical efficacy of the darovasertib and crizotinib combination in first-line and any-line MUM patients.

The darovasertib and crizotinib combination has a manageable adverse event profile in MUM patients (n=68), with a low rate of drug-related serious adverse events (SAEs). Patients reported predominantly Grade 1 or 2 drug-related adverse events (AEs): 31% of patients reported at least one Grade 3 AE; no patients observed a Grade 4 AE; and one patient observed a Grade 5 AE. Four (6%) patients discontinued treatment with either darovasertib or crizotinib due to a drug-related adverse event.

FDA Guidance in Type C Meeting Supports Initiation of Potential Registrational Trial

The Company is targeting to initiate a potential registration-enabling Phase 2/3 clinical trial in Q2 2023 in first-line HLA-A2 negative MUM patients. The Phase 2/3 clinical trial design incorporates guidance and feedback from the FDA following a recent Type C meeting.

The protocol includes an integrated Phase 2/3 open-label study-in-study design in first-line MUM patients with an HLA-A*02:01 negative serotype. The clinical trial design employs a Phase 2 portion with median PFS as a primary endpoint for potential accelerated approval. Patients enrolled in Phase 2 will continue on treatment within the same clinical trial and will be considered together with additional enrolled patients to evaluate overall survival (OS) in support of a potential Phase 3 registrational trial.

In the Phase 2 portion of the clinical trial, approximately 230 patients will be randomized on a 2:1 basis for treatment with the darovasertib and crizotinib combination in the treatment arm or investigators choice in the control arm, selected from a combination of ipilimumab (ipi) and nivolumab (nivo), PD1-targeted monotherapy or DTIC. The treatment arm of the Phase 2 portion includes a nested study to confirm the move forward combination dose for the integrated Phase 2/3 clinical trial – including cohorts at the Phase 2 expansion doses of (i) darovasertib 300 mg BID + crizotinib 200 mg BID and (ii) darovasertib 200 mg BID + crizotinib 200 mg BID. Under the nested study design, patients enrolled in the cohort at the move forward dose will be included within the Phase 2/3 registrational clinical trial. The Phase 2 portion of the clinical trial contemplates an efficacy and safety data set of approximately 200 patients randomized 2:1 with the treatment arm at the move forward dose to support a potential accelerated approval based on median PFS by blinded independent central review (BICR) as a primary endpoint.

Patients enrolled in Phase 2 at the selected dose would continue on treatment and be included in the Phase 3 study analysis, supplemented by enrollment of approximately 120 additional patients into the Phase 3 portion of the clinical trial with 2:1 randomization on the same basis as the Phase 2 portion. Efficacy data from the Phase 3 could support potential approval using median OS as a primary endpoint.

Clinical Data Update – Darovasertib in (Neo)Adjuvant Primary UM

The Company observed further evidence of encouraging clinical activity for darovasertib as neoadjuvant therapy in primary UM, including responses in primary ocular tumor lesions. Data was reported from an ongoing IST evaluating darovasertib in (neo)adjuvant UM, from compassionate use protocol(s) and from the Company’s Phase 1/2 clinical trial evaluating darovasertib as monotherapy and in combination with crizotinib. Best ocular tumor response is reported based on maximal percentage reduction in measured apical height or longest basal diameter.

Collectively, these data further substantiate clinical proof of concept (POC) for the use of darovasertib in the (neo)adjuvant uveal melanoma setting:

Ocular tumor shrinkage by investigator review in 9 of 9 (100%) UM (n=6) or MUM (n=3) patients treated as monotherapy or in combination with crizotinib, including a neoadjuvant UM patient treated with darovasertib with a partial response at one month, and a second neoadjuvant UM patient treated with the darovasertib and crizotinib combination with ~80% ocular tumor shrinkage at four months who was spared enucleation, as described below.

A UM patient who was already blind in one eye from vascular disease developed a large uveal melanoma lesion in his other eye and sought neoadjuvant treatment with a goal to avoid enucleation and potentially preserve vision in the affected eye to prevent blindness. This patient, who remains on therapy, was treated with darovasertib and crizotinib combination under a compassionate use protocol. The preliminary clinical data showed:

observed ~80% ocular tumor shrinkage after four months of treatment and remains on therapy

avoided enucleation of the affected eye, which we believe to be the first reported case of systemic neoadjuvant therapy resulting in eye preservation

prompt responsiveness to treatment, including progressive tumor shrinkage, as determined by investigator measurement of tumor apical height, over each month of treatment, including approximately 30% ocular tumor shrinkage after one month, with ocular lesion size reduced to approach threshold for plaque brachytherapy, and further ocular tumor shrinkage to ~50% after two months, ~70% after three months and ~80% after four months of treatment

improved vision following course of treatment and treatment of a severe cataract: pretreatment vision score was 6/120, where 6/60 is legally blind; post-treatment vision score was 6/5, reflecting a greater than 20-fold improvement and resulting in better than normal vision. Vision scoring was based on AU meter measurement system: 6/6 m = 20/20 ft (normal vision).

The Company is initiating a company-sponsored clinical trial to evaluate darovasertib as monotherapy in (neo)adjuvant UM and is evaluating potential near-term clinical neoadjuvant endpoints such as organ preservation (avoiding enucleation) for large ocular tumors and reduction in radiation dose and/or vision preservation for small or medium ocular tumors.

The Company is also supporting St. Vincent’s Hospital Sydney Limited, which has initiated an ongoing IST captioned as "Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma" (NADOM) (NCT05187884), to evaluate darovasertib monotherapy in a neoadjuvant and adjuvant setting in primary UM patients.

Addressable Patient Population in MUM and UM

The potentially addressable patient population for metastatic uveal melanoma is estimated to include approximately 4,500 patients across the United States and Europe, based on estimated annual incidence, and approximately 14,000 patients in total prevalence in the United States and Europe. (Neo)Adjuvant UM represents a significant expansion opportunity for darovasertib given the potential annual incidence of approximately 8,700 patients aggregate in the United States and Europe, and approximately 100,000 patients in total prevalence in the United States and Europe.

On April 23, 2023 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported further interim results from its Phase 2 clinical trial evaluating darovasertib and crizotinib combination in metastatic uveal melanoma (MUM) patients (ClinicalTrials.gov Identifier: NCT03947385) (Press release, Ideaya Biosciences, APR 23, 2023, View Source [SID1234630400]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The observed efficacy in first-line metastatic uveal melanoma patients – including confirmed ORR of 45% and median PFS of ~ 7 months – is clinically significant and represents a potential paradigm shift for treating MUM patients. The interim data for the darovasertib and crizotinib combination treatment in MUM suggests a compelling clinical efficacy and tolerability profile," said Dr. Meredith McKean, M.D., MPH, Director, Melanoma and Skin Cancer Research at Sarah Cannon Research Institute.

"These clinical data, considered with the FDA’s guidance from our recent Type C meeting, provides IDEAYA with a registrational trial design in first-line HLA-A2 negative MUM patients which includes a path to potential accelerated approval based on median PFS as the primary endpoint," said Dr. Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

There are currently no FDA approved therapies for MUM patients with HLA-A2*02:01 (HLA-A2) negative serotype. Current therapies for MUM have relatively low confirmed overall response rates and short median progression free survival (PFS), highlighting the high unmet medical need. The historical overall response rate (ORR) in MUM clinical trials has generally been reported with a confirmed ORR ranging from approximately 0% to 5%. The historical median PFS in MUM clinical trials has been reported ranging from approximately 2 to 3 months.

Darovasertib (IDE196) is a small molecule, potential first-in-class protein kinase C (PKC) inhibitor. IDEAYA is evaluating the synthetic lethal combination of darovasertib and crizotinib, a small molecule cMET inhibitor, in MUM pursuant to a clinical trial collaboration and drug supply agreement with Pfizer.

Clinical Data Update – Darovasertib and Crizotinib Combination in MUM

The company observed encouraging clinical activity in the Phase 2 clinical trial evaluating the darovasertib and crizotinib combination in first-line and any-line MUM patients. The reported Phase 2 clinical data are based on twenty (20) evaluable first-line and sixty-three (63) evaluable any-line patients enrolled in the darovasertib and crizotinib combination study at the expansion dose of 300 mg twice-a-day darovasertib and 200 mg twice-a-day crizotinib as of September 22, 2022. Reported data are preliminary and based on investigator review from an unlocked database as of the data analyses cutoff date of March 8, 2023. Enrollment in the darovasertib and crizotinib combination expansion dose cohort of the Phase 2 clinical trial is ongoing.

In the twenty (20) evaluable first-line MUM patients in the expansion cohort, the investigator-reviewed data by RECIST 1.1 include:

45% confirmed Overall Response Rate (ORR) in First-Line MUM: 9 of 20 evaluable patients had a confirmed partial response (PR)
90% Disease Control Rate (DCR) in First-Line MUM: 18 of 20 evaluable patients showed disease control, including 9 confirmed PRs, 1 unconfirmed PR and 8 stable disease
~7 months median Progression Free Survival (PFS) in First-Line MUM
In the sixty-three (63) evaluable any-line MUM patients at the expansion dose, the investigator-reviewed data by RECIST 1.1 include:

30% confirmed Overall Response Rate (ORR) in Any-Line MUM: 19 of 63 evaluable patients had a confirmed partial response (PR); the Any-Line MUM patients were heavily pre-treated, with 63% of patients having received 1 or more prior lines of treatment and 43% of patients having received 2 or more prior lines of treatment in the metastatic setting
87% Disease Control Rate (DCR) in Any-Line MUM: 55 of 63 evaluable patients showed disease control, including 19 confirmed PRs, 4 unconfirmed PRs and 32 stable disease
~7 months median Progression Free Survival (PFS) in Any-Line MUM
Observed median PFS increased versus median PFS of ~5 months previously reported in September 2022 with thirty-five (35) evaluable Any-Line MUM patients
There were twenty (20) evaluable hepatic-only MUM patients, including first-line and pre-treated patients with only hepatic metastases, for whom the investigator-reviewed data by RECIST 1.1 include:

35% confirmed Overall Response Rate (ORR) in Hepatic-Only MUM: 7 of 20 evaluable patients had a confirmed partial response (PR)
100% Disease Control Rate (DCR) in Hepatic-Only MUM: 20 of 20 evaluable patients showed disease control, including 7 confirmed PRs, 1 unconfirmed PR and 12 stable disease
~11 months median Progression Free Survival (PFS) in Hepatic-Only MUM
These data demonstrate robust clinical efficacy of the darovasertib and crizotinib combination in first-line and any-line MUM patients.

The darovasertib and crizotinib combination has a manageable adverse event profile in MUM patients (n=68), with a low rate of drug-related serious adverse events (SAEs). Patients reported predominantly Grade 1 or 2 drug-related adverse events (AEs): 31% of patients reported at least one Grade 3 AE; no patients observed a Grade 4 AE; and one patient observed a Grade 5 AE. Four (6%) patients discontinued treatment with either darovasertib or crizotinib due to a drug-related adverse event.

FDA Guidance in Type C Meeting Supports Initiation of Potential Registrational Trial

IDEAYA is targeting to initiate a potential registration-enabling Phase 2/3 clinical trial in Q2 2023 in first-line HLA-A2 negative MUM patients. The Phase 2/3 clinical trial design incorporates guidance and feedback from the FDA following a recent Type C meeting.

The protocol includes an integrated Phase 2/3 open-label study-in-study design in first-line MUM patients with an HLA-A*02:01 negative serotype. The clinical trial design employs a Phase 2 portion with median PFS as a primary endpoint for potential accelerated approval. Patients enrolled in Phase 2 will continue on treatment within the same clinical trial and will be considered together with additional enrolled patients to evaluate OS in support of a potential Phase 3 registrational trial.

In the Phase 2 portion of the clinical trial, approximately 230 patients will be randomized on a 2:1 basis for treatment with the darovasertib and crizotinib combination in the treatment arm or investigators choice in the control arm, selected from a combination of ipilimumab (ipi) and nivolumab (nivo), PD1-targeted monotherapy or DTIC. The treatment arm of the Phase 2 portion includes a nested study to confirm the move forward combination dose for the integrated Phase 2/3 clinical trial – including cohorts at the Phase 2 expansion doses of (i) darovasertib 300 mg BID + crizotinib 200 mg BID and (ii) darovasertib 200 mg BID + crizotinib 200 mg BID. Under the nested study design, patients enrolled in the cohort at the move forward dose will be included within the Phase 2/3 registrational clinical trial. The Phase 2 portion of the clinical trial contemplates an efficacy and safety data set of approximately 200 patients randomized 2:1 with the treatment arm at the move forward dose to support a potential accelerated approval based on median PFS by blinded independent central review (BICR) as a primary endpoint.

Patients enrolled in Phase 2 at the selected dose would continue on treatment and be included in the Phase 3 study analysis, supplemented by enrollment of approximately 120 additional patients into the Phase 3 portion of the clinical trial with 2:1 randomization on the same basis as the Phase 2 portion. Efficacy data from the Phase 3 could support potential approval using median OS as a primary endpoint.

Clinical Data Update – Darovasertib in (Neo)Adjuvant Primary UM

The company observed further evidence of encouraging clinical activity for darovasertib as neoadjuvant therapy in primary uveal melanoma (UM), including responses in primary ocular tumor lesions. Data was reported from an ongoing investigator sponsored trial (IST) evaluating darovasertib in (neo)adjuvant uveal melanoma, from compassionate use protocol(s) and from the company’s Phase 1/2 clinical trial evaluating darovasertib as monotherapy and in combination with crizotinib. Best ocular tumor response is reported based on maximal percentage reduction in measured apical height or longest basal diameter.

Collectively, these data further substantiate clinical proof of concept (PoC) for the use of darovasertib in the (neo)adjuvant uveal melanoma setting:

Ocular tumor shrinkage by investigator review in 9 of 9 (100%) UM (n=6) or MUM (n=3) patients treated as monotherapy or in combination with crizotinib, including a neoadjuvant UM patient treated with darovasertib with a partial response at 1 month, and a second neoadjuvant UM patient treated with the darovasertib and crizotinib combination with ~80% ocular tumor shrinkage at 4 months who was spared enucleation, as described below.
A UM patient who was already blind in one eye from vascular disease developed a large uveal melanoma lesion in his other eye and sought neoadjuvant treatment with a goal to avoid enucleation and potentially preserve vision in the affected eye to prevent blindness. This patient, who remains on therapy, was treated with darovasertib and crizotinib combination under a compassionate use protocol. The preliminary clinical data showed:
observed ~80% ocular tumor shrinkage after 4 months of treatment and remains on therapy
avoided enucleation of the affected eye, which we believe to be a first reported case of systemic neoadjuvant therapy resulting in eye preservation
prompt responsiveness to treatment, including progressive tumor shrinkage, as determined by investigator measurement of tumor apical height, over each month of treatment, including approximately 30% ocular tumor shrinkage after 1 month, with ocular lesion size reduced to approach threshold for plaque brachytherapy, and further ocular tumor shrinkage to ~50% after 2 months, ~70% after 3 months and ~80% after 4 months of treatment
improved vision following course of treatment and treatment of a severe cataract: pretreatment vision score was 6/120, where 6/60 is legally blind; post-treatment vision score was 6/5, reflecting a greater than 20-fold improvement and resulting in better than normal vision. Vision scoring was based on AU meter measurement system: 6/6 m = 20/20 ft (normal vision).
"These additional clinical data underscore the potential for darovasertib as a (neo)adjuvant approach for the treatment of uveal melanoma patients. If clinically validated, this approach could significantly improve current primary treatment paradigms, which typically include radiotherapies and/or enucleation of the eye," said Prof. Anthony Joshua, MBBS Ph.D. FRACP, Head of the Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent’s Hospital/Garvan Medical Research Institute, Sydney, Australia.

IDEAYA is initiating a company-sponsored clinical trial to evaluate darovasertib as monotherapy in (neo)adjuvant uveal melanoma and is evaluating potential near-term clinical neoadjuvant endpoints such as organ preservation (avoiding enucleation) for large ocular tumors and reduction in radiation dose and/or vision preservation for small or medium ocular tumors.

IDEAYA is also supporting St. Vincent’s Hospital Sydney Limited, which has initiated an ongoing IST captioned as "Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma" (NADOM) (NCT05187884), to evaluate darovasertib monotherapy in a neoadjuvant and adjuvant setting in primary UM patients.

Addressable Patient Population in MUM and UM

The potentially addressable patient population for metastatic uveal melanoma is estimated to include approximately 4,500 patients across U.S. and Europe, based on estimated annual incidence, and approximately 14,000 patients in total prevalence in the US and Europe. (Neo)Adjuvant UM represents a significant expansion opportunity for darovasertib – with a potential annual incidence of approximately 8,700 patients aggregate in U.S. and Europe, and approximately 100,000 patients in total prevalence in the U.S. and Europe.

IDEAYA owns or controls all commercial rights in darovasertib, including in MUM and in UM, subject to certain economic obligations pursuant to the Novartis exclusive, worldwide license.

IDEAYA Investor Webcast and Conference Call

IDEAYA will host an investor webcast and conference tomorrow morning, Monday, April 24, 2023 at 8:00 am Eastern Time (ET), to present the further darovasertib and crizotinib Phase 2 clinical efficacy and tolerability data in metastatic uveal melanoma, and the potential registrational clinical trial design based on guidance and feedback from the recent FDA Type C meeting. The company will also provide a clinical data update for darovasertib in neoadjuvant uveal melanoma.

Presenters at the investor webcast and conference call will include Dr. Meredith McKean, M.D., MPH, Director, Melanoma and Skin Cancer Research at Sarah Cannon Research Institute, Prof. Anthony Joshua, MBBS Ph.D. FRACP, Head of the Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent’s Hospital/Garvan Medical Research Institute, Sydney, Australia, and Prof. Mark Shackleton, MBBS, Ph.D., FRACP, Professor of Oncology, Monash University, Director of Oncology, Alfred Health, Chair, Melanoma and Skin Cancer Trials, Melbourne, Australia, each of whom are key opinion leaders and clinical investigators. Yujiro S. Hata, Chief Executive Officer of IDEAYA Biosciences, and Darrin Beaupre, M.D., Ph.D., Chief Medical Officer of IDEAYA Biosciences, will also present.

IDEAYA’s darovasertib investor webcast presentation, as well as an updated corporate presentation, which incorporates the updated darovasertib clinical data as well as IDE397, IDE161 and Werner Helicase program updates from AACR (Free AACR Whitepaper) 2023, will be available on the company’s website, at its Investor Relations portal (View Source) in advance of the investor webcast presentation at approximately 6:00 am ET.

Corporate Updates
IDEAYA had cash, cash equivalents and marketable securities of approximately $373 million as of December 31, 2022, which it currently projects will be sufficient to fund its planned operations into 2026.

On April 23, 2023 Singapore based SCG Cell Therapy Pte Ltd (SCG), a clinical-stage biotechnology company developing novel immunotherapies for infectious diseases and their associated cancers, reported that late-breaking data from the company’s TCR-T therapy pipeline – SCG101, will be presented at the International Society for Cell & Gene Therapy (ISCT) in Paris, France on 1 June (Press release, SCG Cell Therapy, APR 23, 2023, View Source;gene-therapy-isct-highlighting-promising-antitumor-and-antiviral-activities-of-scg101-in-treating-hbv-related-hepatocellular-carcinoma-301804926.html [SID1234630399]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"These exciting new data being presented at ISCT continue to reinforce the potential for viral antigen specific TCR-T product to effectively treat infection-associated solid tumour indications like HBV-related hepatocellular carcinoma," said Frank Wang, Chief Executive Officer of SCG Cell Therapy. "The clinical data shows exceptional efficacy of this novel TCR-T cell therapy. Thus far, SCG101 has shown to produce robust and durable anti-tumour and antiviral responses and we look forward to providing additional updates on this program as the trial progresses."

SCG101 is an autologous TCR-T cell therapy targeting specific hepatitis B surface antigen (HBsAg) epitopes. The late-breaking data to be presented at ISCT demonstrated positive efficacy of SCG101 as a monotherapy in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), achieving partial response (PR) after a single dose of SCG101 with durable tumour response observed. Serum HBsAg significantly decreased and the expression of HBsAg in hepatocyte dropped to undetectable.

In June 2022, SCG Cell Therapy presented the first clinical proof-of-concept data demonstrating the mechanism of action of a HBsAg-specific TCR-T cell therapy, SCG101, at the International Liver Congress (ILC) 2022. The data showed precise target engagement and cell proliferation, and demonstrated antiviral activity and tumour control. Sixty-six percent of patients with advanced HBV-related HCC observed lesion shrinkage as well as significant serum HBsAg reduction (> 2 log) within 28 days from single dose monotherapy SCG101 treatment.

Presentation Details:
Title: Infected hepatocyte clearance and sustained tumour regression by first-in-class HBsAg-specific TCR-T (SCG101) therapy for HBV-related HCC
Presenter: 1093
Abstract Number: 3907176
Date and Time: 1 June, 2023

About SCG101
SCG101, an autologous T-cell receptor (TCR) T cell therapy, is an investigational cell therapy product targeting specific epitopes of hepatitis B surface antigen (HBsAg). Utilizing SCG’s proprietary GianTTM technology, high affinity and high avidity natural TCR can be identified against intracellular antigens expressed through major histocompatibility complex (MHC) in solid tumours. Preclinical studies of SCG101 demonstrated tumour inhibition and HBV cccDNA eradication. SCG101 was granted clinical trial approvals by the U.S Food and Drug Administration (FDA), China National Medical Products Administration (NMPA) and Singapore Health Science Authority (HSA) for patient with HBV-related HCC. A Phase 1/2 clinical trial evaluating SCG101 is ongoing.

About Hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is the most common type of liver cancer. It is estimated more than 905,000 new cases of liver cancer and more than 830,100 deaths from the disease globally in 2020, making it one of the leading causes of cancer deaths around the world [1]. Chronic hepatitis B virus (HBV) infection accounts for at least 50% of cases of HCC worldwide [2]. HCC is typically diagnosed at an advanced stage and is associated with a poor prognosis. The five-year survival rate of less than 15%.