On April 30, 2024 Valerio Therapeutics S.A. (Euronext Growth Paris: ALVIO), hereafter "Valerio Therapeutics" or the "Company"), a clinical-stage biotechnology company specializing in the development of innovative drugs targeting tumor DNA Damage Response (DDR) and driver oncogenes, reported its consolidated results for the fiscal year ending December 31, 2023 (Press release, Valerio Therapeutics, APR 30, 2024, View Source [SID1234642467]).

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Dr. Shefali Agarwal, Chairwoman of the Board of Directors and CEO, stated: "I am delighted to announce that the first patient has been dosed with VIO-01 in the first-in-human study VIO-01-101. VIO-01 is the latest optimized drug candidate derived from Valerio Therapeutics’ proprietary PlatON platform of DNA decoy therapeutics, specifically designed to revolutionize cancer treatment. VIO-01, as a next-generation pan-DDR DNA decoy, represents a paradigm shift in therapeutic approach. It is meticulously crafted to not only abrogate multiple DNA repair pathways but also to unleash a potent immune response by activating the STING pathway which plays a pivotal role in identifying DNA abnormalities and mobilizing the immune system to target and eliminate cancer cells. Our commitment to advancing science, pushing boundaries, and making a meaningful impact on cancer treatment remains unwavering. Together, with the support of our dedicated team and the medical community, we look forward to bringing VIO-01 one step closer to transforming the landscape of cancer care."

FY 2023 FINANCIAL RESULTS*

Consolidated income statement (IFRS)
In thousands of euros

31/12/2023 31/12/2022
Revenues 1,800 1,443
Operating expenses, of which:
R&D expenses

(21,054) (19,008)
(11,054)

Other recurring operating income 200 450
Recurring operating income/loss (19,053) (17,115)
Other non-recurring operating income and expenses (1,234) 389
Operating income/loss after income from equity affiliates (20,288) (16,727)
Financial result (39) (2,549)
Tax (17) (285)
Loss (20,344) (19,562)
*Audit procedures on the consolidated accounts have been carried out. The certification report will be issued once the management report has been verified.

Revenues for full-year 2023 totaled €1,8 million corresponding to lump-sum royalties due from Biogen under a license agreement for a non-strategic product.

Operating expenses rose from €19.0 million in 2022 to €21.1 million in 2023, mainly due to:

Personnel expenses, which increase from €8.6 million to €9.3 million, as a result of the reinforcement of the teams, and more specifically to the recruitment of highly qualified scientists as well as the indemnities paid to the former employees who left the Group in 2023.
External expenses increased from €9.4 million to €10.3 million, due to R&D activities, with a focus in 2023 on the clinical development of AsiDNA and on the optimization and preclinical development of VIO-01.
The financial result was a loss of (39) thousand euros.

After taking into account these various items of income and expense, the net result is a loss of €20.34 million compared to a loss of €19.56 million recorded in the previous year.

FINANCIAL STRUCTURE

As of December 31, 2023, the Group had a cash position of €6.8 million, compared with €14.6 million at December 31, 2022. The outstanding financial debt at the end of 2023 amounted to €9.0 million, which includes state-backed loans obtained in February 2021.

The financial statements have been prepared on a going concern basis. This principle has been retained by the Board of Directors on the basis of a cash position of 6.8 million euros on December 31, 2023 and the financing commitments received from its main shareholders Invus and Financière de la Montagne, in an amount of 5 million euros. The Group will thus be able to finance its activities at least until the end of the fourth quarter of 2024 on the basis of its financing plan.

2023 HIGHLIGHTS AND RECENT DEVELOPMENTS

AsiDNA

AsiDNA is a first-in-class DNA Decoy which traps and sequesters DNA-PK, a complex of proteins involved in the DNA Damage Response. AsiDNA thus induces inhibition of DNA-PK-dependent DNA repair in tumor cell, which nevertheless continues its replication cycle, but with damaged DNA, thus leading to cell death. AsiDNA is used in combination with other tumor DNA damaging agents such as radiotherapy and chemotherapy, or in combination with inhibitors of a specific repair pathway such as PARPi or other targeted therapies, to increase their efficacy, notably by abrogating any resistance to these treatments, without increasing toxicity. AsiDNA specifically targets tumor cells and has a very favorable safety profile in humans observed in four Phase 1/1b clinical studies.

The Company continued the clinical development of AsiDNA in 2023.

Given the limited efficacy observed during phase 1 clinical trials especially as a monotherapy, it was not considered beneficial for patients to further pursue clinical development of AsiDNA or initiate a phase 2 study. Furthermore, AsiDNA is assumed to generate no revenue and only have minor carrying costs for company industrial property. For all these reasons, it was decided to deprioritize AsiDNA clinical investigation to focus efforts on development of VIO-01, our second-generation drug candidate.

In clinical development

The company initiated a multi-center Phase 1b/2 trial to evaluate the safety and efficacy of AsiDNA in combination with the PARP inhibitor Olaparib in patients with epithelial ovarian cancer, breast cancer and metastatic castration-resistant prostate cancer who have progressed despite initial treatment with PARP inhibitors. This clinical trial started in January 2023, with the activation of the first clinical study site in the United States, Next Oncology in San Antonio.

In addition, during the first half of the year, Valerio Therapeutics continued its two trials conducted in collaboration with two academic research centers of excellence in oncology:

The Revocan phase 1b/2 investigator sponsored trial evaluating the addition of AsiDNA to combat PARP inhibitor resistance in second-line maintenance treatment of recurrent ovarian cancer.
The Phase 1b/2 trial evaluating AsiDNA in combination with radiotherapy in recurrent high-grade glioma in children, an indication with a particularly poor prognosis.
vio-01

VIO-01, formerly OX425, is a Pan-DDR DNA Decoy Targeting Multiple Proteins & Repair Pathways and represents the most optimal drug candidate selected to enter preclinical development. VIO-01 traps several DDR Proteins Inhibiting Different DNA Repair Pathways. VIO-01 reaches the nucleus and acts as a decoy for several DNA repair enzymes. It has an increased resistance to nucleases and plasmatic stability.

Valerio Therapeutics presented new preclinical data confirming the pan-DDR DNA decoy effect of VIO-01 and the high anti-tumor activity in tumor models independently from the homologous recombination repair status on April 19, 2023, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. Also, the Company presented new preclinical data confirming VIO-01’s capability to abrogate several DNA repair pathways and induce a drug-driven synthetic lethality, without the need of a combined treatment.

VIO-01 underwent late-stage IND-enabling preclinical development in 2023, with the execution of regulatory toxicology and ADME/PK studies. This package allowed IND submission to FDA followed by approval to start first-in-human clinical trial.

NEXT Oncology San Antonio, the first site for the Phase 1/2 (VIO-01-101) study investigating VIO-01 has been activated and has dosed the first patient.

3rd generation of PlatON platform

Valerio Therapeutics continued to optimize the PlatON platform to develop more potent assets coupled to innovative technologies, with the objective to combine PlatON platform’s DNA decoys with the targeted protein degradation strategy offered by PROTACs (PROteolysis-TArgeting Chimeras) technology. PROTACs technology and other tumor specific targeting options may be a novel class of heterobifunctional molecules that can selectively degrade target proteins within cells. This approach offers several advantages over the other molecules involved in modulating the DNA damage response, such as increased selectivity and reduced toxicity. This specific strategy involves generating DecoyTAC combining our vectorized DNA decoy molecules capable of efficient cell penetration with a linker+E3 ligand promoting the complete degradation of the target proteins, thereby presenting a novel mechanism of action.

The exploration of the convergence of PROTACs and DNA Decoys aims to not only propose new therapeutic modalities against DDR proteins but also against transcription factor proteins that are challenging to target. Through these efforts, the Company strives to advance the field of oncology drug development and contribute to the treatment of cancer patients.

Evolution of the R&D portfolio

Changes from the portfolio presented in the 2022 annual financial report are as follows:

The Phase 1/2 of the trial AsiDNA in the U.S., in combination with the PARP inhibitor Olaparib enrolled three patients in 2023.
Postponement of the preliminary results of the Revocan study to the first half of 2023, instead of the second half of 2022, due to slowed enrollment.
Preclinical development of VIO-01 (formerly OX425), with the execution of regulatory toxicology and ADME/PK studies and the filing of an Investigational New Drug (IND) application with the FDA in October 2023.

Governance

The Annual General Meeting of June 6, 2023, renewed the terms of Financière de la Montagne, represented by Mr. Nicolas Trebouta, and Mr. Robert Coleman as directors for three years.

The Board of Directors is currently composed of 7 members, 6 men and 1 woman, including 3 independent members.

2024 OUTLOOK

In 2024, the Company will continue to pursue its value creation strategy based on the development of its therapeutic innovations until proof of concept in humans, with the following main milestones:

VIO-01

Execute the clinical study VIO-01-101 for VIO-01
Recruitment and dosing of patients for the Phase 1/2 (VIO-01-101).

AsiDNATM

Deprioritization of AsiDNA clinical investigation to focus efforts on developing VIO-01, our second-generation development candidate.
PlatON

Continued optimization of PlatON platform by developing DecoyTAC, leveraging the unique DNA Decoy MoA and the targeted protein degradation (PROTAC), and expanding the targets beyond DDR.

On April 30, 2024 Mythic Therapeutics, a clinical-stage biotechnology company committed to the development of next-generation antibody-drug conjugate (ADC) therapies for the treatment of a wide range of cancers, reported the publication of preclinical data highlighting the differentiating properties of its investigational cMET-targeting ADC, MYTX-011, in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Mythic Therapeutics, APR 30, 2024, View Source;utm_medium=rss&utm_campaign=mythic-therapeutics-announces-publication-of-preclinical-data-highlighting-the-differentiating-properties-of-mytx-011-in-molecular-cancer-therapeutics [SID1234642466]).

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"The potential of novel ADC technologies to enhance payload delivery to tumors is relatively underexplored compared to advances in linker-payload technology and target selection," said Nimish Gera, Ph.D., lead author of the paper and Scientific Co-founder, Vice President of Biologics at Mythic. "We believe that engineering pH-dependent binding could be a particularly compelling strategy for ADCs targeting medium to low levels of cMET expression in patients. We’re pleased to publish this study illustrating how the properties of MYTX-011, including its potential for increased on-target potency, enhanced tolerability, longer half-life and higher efficacy, may enable this therapy to serve patients with a broad range of cMET expression who otherwise have limited treatment options. We look forward to continuing to evaluate MYTX-011 in our ongoing Phase 1 clinical trial."

The study demonstrated that incorporation of pH-dependent binding in the antibody component of a cMET targeting ADC can overcome the requirement for high cMET expression on tumors, an innovation that has the potential to benefit a broader population of patients with lower cMET levels. MYTX-011 drove four-fold higher net internalization than a non-pH engineered parent ADC in non-small cell lung cancer (NSCLC) cells and showed increased cytotoxicity against a panel of cell lines from various solid tumors, including head and neck, gastric, pancreatic, esophageal, bladder, kidney and skin cancer. A single dose of MYTX-011 showed at least three-fold higher efficacy than a benchmark ADC in mouse xenograft models of NSCLC ranging from low to high cMET expression. Additionally, MYTX-011 showed improved pharmacokinetics over parent and benchmark ADCs. In a repeat dose toxicology study, MYTX-011 exhibited a toxicity profile similar to other MMAE-based ADCs.

MYTX-011 is currently being evaluated in the Phase 1 KisMET-01 clinical trial, a first-in-human, open-label, multi-center, dose escalation and dose expansion study enrolling patients with locally advanced, recurrent or metastatic NSCLC (NCT05652868).

About MYTX-011

MYTX-011, an investigational cMET-targeting antibody-drug conjugate (ADC), leverages Mythic’s innovative FateControl technology, which allows ADCs to actively navigate inside of cells, potentially increasing delivery of anti-cancer agents to tumor cells with less impact on healthy cells. This breakthrough approach takes the next step beyond linker-payload technologies and is designed to improve ADC efficacy against a broad set of molecular targets and patient profiles. MYTX-011 is currently being evaluated in the Phase 1 KisMET-01 clinical trial, a first-in-human, open-label, multi-center, dose escalation and dose expansion study enrolling patients with locally advanced, recurrent or metastatic NSCLC (NCT05652868).

On April 30, 2024 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported that senior leadership plans to present at the following conferences (Press release, Iovance Biotherapeutics, APR 30, 2024, View Source [SID1234642465]):

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Chardan Annual Genetic Medicines & Cell Therapy Manufacturing Summit
Fireside Chat: April 30, 2024 at 2:30 p.m. ET
Virtual
The Citizens JMP Life Sciences Conference
Fireside Chat: May 13, 2024 at 2:00 p.m. ET
New York, NY
The live and archived webcasts will be available at View Source

On April 30, 2024 Incyte (Nasdaq:INCY) reported 2024 first quarter financial results, and provides a status update on the Company’s clinical development portfolio (Press release, Incyte, APR 30, 2024, View Source [SID1234642464]).

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"In the first quarter of 2024, total revenues grew 9% year-over-year driven by patient demand growth in the U.S. for Opzelura (ruxolitinib) cream and Jakafi (ruxolitinib). As anticipated, the revenue growth during the quarter was offset by an inventory drawdown for Jakafi and the typical first quarter net pricing dynamics," said Hervé Hoppenot, Chief Executive Officer, Incyte. "We made important progress with our clinical pipeline including the initiation of two Phase 1 studies evaluating our JAK2V617F inhibitor and KRASG12D inhibitor. We also recently announced an agreement to acquire Escient Pharmaceuticals, pending the appropriate regulatory review process. Escient’s lead compound EP262, is a first-in-class, potent, highly selective, once-daily small molecule designed to block mast cell activation, independent from IgE. We believe this novel mechanism has broad clinical utility in a number of conditions including chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU) and other diseases."

Key First Quarter 2024 Company Updates

•In February 2024, Incyte announced that the U.S. Food and Drug Administration (FDA) accepted for Priority Review the Biologics License Application (BLA) for axatilimab, an anti-CSF-1R antibody, for the treatment of chronic graft-versus-host disease (GVHD) after failure of at least two prior lines of systemic therapy.
•In February 2024, Incyte entered into an asset purchase agreement with MorphoSys AG which gave Incyte exclusive global rights for tafasitamab, a humanized Fc-modified CD19-targeting immunotherapy marketed in the U.S. as Monjuvi (tafasitamab-cxix) and outside of the U.S. as Minjuvi (tafasitamab).
•In March 2024, multiple abstracts featuring data from Incyte’s dermatology portfolio were presented at the 2024 American Academy of Dermatology (AAD) Annual Meeting, including two late-breaking oral presentations for ruxolitinib cream (Opzelura) in hidradenitis suppurativa (HS) and povorcitinib in prurigo nodularis (PN).
•In April 2024, Incyte and China Medical System Holdings Limited announced the Companies entered into a Collaboration and License Agreement, through a wholly-owned dermatology medical aesthetic subsidiary CMS Skinhealth, for the development and commercialization of povorcitinib, a selective oral JAK1 inhibitor, in Mainland China, Hong Kong, Macau, Taiwan Region and eleven Southeast Asian countries.
•In April 2024, Incyte and Escient Pharmaceuticals, a clinical-stage drug development company advancing novel small molecule therapeutics for systemic immune and neuro-immune disorders, entered into a definitive agreement under which Incyte has agreed to acquire Escient and its clinical development portfolio, including EP262, a first-in-class, potent, highly selective, once-daily small molecule antagonist of Mas-related G protein-coupled receptor (MRGPRX2) and EP547, a first-in-class oral MRGPRX4 antagonist. Under the terms of the agreement, Incyte will acquire Escient and its assets for $750 million plus Escient’s net cash remaining at the close of the transaction, subject to customary adjustments. The acquisition is subject to clearance under the Hart-Scott-Rodino Act, among other customary conditions, and will become effective promptly following the satisfaction or waiver of these conditions.
Jakafi:
Net product revenues for the first quarter 2024 of $572 million (-1% Y/Y):
▪Total paid patients increased 5% in the first quarter of 2024 versus the same quarter in the prior year, with growth across all indications and leading to the highest quarterly paid patient demand for Jakafi since launch.
▪Patients on free drug in the fourth quarter of 2023 gradually returned to paid demand during the first quarter of 2024; as a result, the percent of patients on free drug returned to more normalized levels during the first quarter of 2024.
▪Channel inventory at the end of the first quarter of 2024 decreased by approximately $55 million versus the fourth quarter of 2023.
Opzelura:
Net product revenues for the first quarter 2024 of $86 million (+52% Y/Y):
▪Net product revenues growth in the first quarter of 2024 were driven by patient demand, refills and expansion in payer coverage as the launch in atopic dermatitis (AD) and vitiligo continues.
▪Net product revenues of $6 million in the first quarter of 2024 in Europe where the launch is ongoing in Germany, Austria and initial uptake has begun in France.
Additional Pipeline Updates
Myeloproliferative Neoplasms (MPNs) and Graft-Versus-Host Disease (GVHD) – key highlights
▪Combination trials of ruxolitinib twice daily (BID) with zilurgisertib (INCB000928) and BETi (INCB057643) are ongoing and continue to enroll. A Phase 3 study for BETi is anticipated to initiate in the second half of 2024 and clinical proof-of-concept for zilurgisertib is anticipated by mid-2024.
▪The Phase 1 studies evaluating INCA033989 (mCALR) and INCB100658 (JAK2V617F) are ongoing and enrolling patients.

MPN and GVHD Programs Indication and status
Ruxolitinib XR (QD)
(JAK1/JAK2) Myelofibrosis, polycythemia vera and GVHD
Ruxolitinib + zilurgisertib
(JAK1/JAK2 + ALK2) Myelofibrosis: Phase 2
Ruxolitinib + INCB57643
(JAK1/JAK2 + BET) Myelofibrosis: Phase 2
Ruxolitinib + CK08041
(JAK1/JAK2 + CB-Tregs)
Myelofibrosis: Phase 1
Axatilimab (anti-CSF-1R)2
Chronic GVHD: Pivotal Phase 2 (third-line plus therapy) (AGAVE-201); BLA under review in the U.S.
Ruxolitinib + axatilimab2
(JAK1/JAK2 + anti-CSF-1R)
Chronic GVHD: Phase 2 in preparation
Steroids + axatilimab2
(Steroids + anti-CSF-1R)
Chronic GVHD: Phase 3 in preparation
INCA033989
(mCALR) Myelofibrosis, essential thrombocythemia: Phase 1
INCB160058
(JAK2V617Fi) Phase 1

1 Development collaboration with Cellenkos, Inc.
2 Clinical development of axatilimab in GVHD conducted in collaboration with Syndax Pharmaceuticals.
Other Hematology/Oncology – key highlights
•In January 2024, Incyte highlighted promising early clinical efficacy data for its selective small molecule inhibitor of CDK2 (INCB123667), which demonstrated its potential use as monotherapy or combination therapy for late-stage cancers. In a Phase 1 study of INCB123667, early clinical activity was observed with several partial responses (PR) achieved in patients with amplification/over expression of CCNE1, a cell cycle regulator and potential predictive biomarker. Tumor shrinkage was observed across multiple tumor types, including CCNE1+ patients with ovarian cancer. The safety profile of INCB123667 aligns with the mechanism of action. Additional data is expected to be presented in 2024.
•In April 2024, Incyte presented new preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 highlighting its KRASG12D inhibitor (INCB161734). INCB161734 is a potent, selective, and orally bioavailable KRAS G12D inhibitor which is efficacious against KRAS G12D mutant tumors in preclinical models. The potential benefit of INCB161734 for patients with KRAS G12D mutant disease is under investigation in an ongoing Phase 1 study. The KRASG12D mutation is found in 40% of pancreatic ductal adenocarcinoma patients, 15% of colorectal cancer patients, and 5% of non-small cell lung cancer patients and with no approved G12D-targeting agents, represents a significant medical need.
3

Oncology Programs Indication and status
Pemigatinib (Pemazyre)
(FGFR1/2/3)
Myeloid/lymphoid neoplasms (MLN): approved in the U.S. and Japan
Cholangiocarcinoma (CCA): Phase 3 (FIGHT-302)
Tafasitamab (Monjuvi/Minjuvi)
(CD19)
Relapsed or refractory diffuse large B-cell lymphoma (DLBCL): Phase 3 (B-MIND)
First-line DLBCL: Phase 3 (frontMIND)
Relapsed or refractory follicular lymphoma (FL) and relapsed or refractory marginal zone lymphoma (MZL): Phase 3 (inMIND)
Retifanlimab (Zynyz)1
(PD-1)
Merkel cell carcinoma (MCC): approved in the U.S.
Squamous cell anal cancer (SCAC): Phase 3 (POD1UM-303)
Non-small cell lung cancer (NSCLC): Phase 3 (POD1UM-304)
MSI-high endometrial cancer: Phase 2 (POD1UM-101, POD1UM-204)
INCB99280
(Oral PD-L1) Solid tumors (combination): Phase 1
Solid tumors (monotherapy): Phase 2
Cutaneous squamous cell carcinoma (cSCC): Phase 2
INCB99318
(Oral PD-L1) Solid tumors: Phase 1
INCB123667
(CDK2i) Solid tumors with Amplification/ Overexpression of CCNE1: Phase 1
INCB161734
(KRASG12D) Advanced metastatic solid tumors with a KRAS G12D mutation: Phase 1

1 Retifanlimab licensed from MacroGenics.
Inflammation and Autoimmunity (IAI) – key highlights
Dermatology
Opzelura
▪In March 2024, Incyte presented data at the 2024 AAD Annual Meeting from its randomized, placebo-controlled, Phase 2 study evaluating the safety and efficacy of ruxolitinib cream (Opzelura) in adults with mild/moderate HS. At Week 16, patients receiving ruxolitinib cream 1.5% twice daily (BID) had significantly greater decreases from baseline versus placebo in total abscess and inflammatory nodule (AN) count, the primary endpoint of the study. The overall safety profile of ruxolitinib cream was consistent with previous data, and no new safety signals were observed. A Phase 3 study is currently being evaluated.
▪Ruxolitinib cream in other indications: Phase 2 studies in lichen planus and lichen sclerosus have completed enrollment. Two Phase 3 trials evaluating ruxolitinib cream in PN are ongoing.
Povorcitinib (INCB54707)
▪The Phase 2, randomized, double-blind, placebo-controlled, dose ranging study evaluating the efficacy and safety of povorcitinib in participants with PN were presented at the 2024 AAD Annual Meeting with the study meeting its primary and secondary endpoints following 16 weeks of treatment across all dosing groups, reinforcing povorcitinib’s potential role in treating PN. A Phase 3 study in PN is being planned.
▪Asthma and chronic spontaneous urticaria: Two Phase 2 trials in asthma and chronic spontaneous urticaria are enrolling.
4

IAI and Dermatology Programs Indication and status
Ruxolitinib cream (Opzelura)1
(JAK1/JAK2)
Atopic dermatitis: Phase 3 pediatric study (TRuE-AD3)
Vitiligo: Approved in the U.S. and Europe
Lichen planus: Phase 2
Lichen sclerosus: Phase 2
Hidradenitis suppurativa: Phase 2; Phase 3 being evaluated
Prurigo nodularis: Phase 3 (TRuE-PN1, TRuE-PN2)
Ruxolitinib cream + UVB
(JAK1/JAK2 + phototherapy) Vitiligo: Phase 2
Povorcitinib
(JAK1) Hidradenitis suppurativa: Phase 3 (STOP-HS1, STOP-HS2)
Vitiligo: Phase 3 (STOP-V1, STOP-V2)
Prurigo nodularis: Phase 3 to start in 2024
Asthma: Phase 2
Chronic spontaneous urticaria: Phase 2
INCA034460
(anti-IL-15Rβ) Vitiligo: Phase 1 initiated

1 Novartis’ rights to ruxolitinib outside of the United States under our Collaboration and License Agreement with Novartis do not include topical administration.
Other
Other Program Indication and Phase
Zilurgisertib
(ALK2) Fibrodysplasia ossificans progressiva: Pivotal Phase 2

Discovery and other early development
Modality Candidates
Monoclonal antibodies
INCAGN2385 (LAG-3)1, INCAGN2390 (TIM-3)1
Bi-specific antibodies
INCA32459 (LAG-3xPD-1)2, INCA33890 (TGFβR2xPD-1)2

1 Discovery collaboration with Agenus.
2 Development in collaboration with Merus.
Partnered
Partnered Programs Indication and Phase
Ruxolitinib (Jakavi)1
(JAK1/JAK2)
Acute and chronic GVHD: Approved in Europe and Japan
Baricitinib (Olumiant)2
(JAK1/JAK2)
AD: Approved in Europe and Japan
Severe alopecia areata (AA): Approved in the U.S., Europe and Japan
Capmatinib (Tabrecta)3
(MET)
NSCLC (with MET exon 14 skipping mutations): Approved in the U.S., Europe and Japan

1 Ruxolitinib (Jakavi) licensed to Novartis ex-U.S. for use in hematology and oncology excluding topical administration.
2 Baricitinib (Olumiant) licensed to Lilly: approved as Olumiant in multiple territories globally for certain patients with moderate-to-severe rheumatoid arthritis; approved as Olumiant in EU and Japan for certain patients with atopic dermatitis.
3 Capmatinib (Tabrecta) licensed to Novartis.
5

2024 First Quarter Financial Results
The financial measures presented in this press release for the three months ended March 31, 2024 and 2023 have been prepared by the Company in accordance with U.S. Generally Accepted Accounting Principles ("GAAP"), unless otherwise identified as a Non-GAAP financial measure. Management believes that Non-GAAP information is useful for investors, when considered in conjunction with Incyte’s GAAP disclosures. Management uses such information internally and externally for establishing budgets, operating goals and financial planning purposes. These metrics are also used to manage the Company’s business and monitor performance. The Company adjusts, where appropriate, for expenses in order to reflect the Company’s core operations. The Company believes these adjustments are useful to investors by providing an enhanced understanding of the financial performance of the Company’s core operations. The metrics have been adopted to align the Company with disclosures provided by industry peers.
Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used in conjunction with and to supplement Incyte’s operating results as reported under GAAP. Non-GAAP measures may be defined and calculated differently by other companies in our industry.
As changes in exchange rates are an important factor in understanding period-to-period comparisons, Management believes the presentation of certain revenue results on a constant currency basis in addition to reported results helps improve investors’ ability to understand its operating results and evaluate its performance in comparison to prior periods. Constant currency information compares results between periods as if exchange rates had remained constant period over period. The Company calculates constant currency by calculating current year results using prior year foreign currency exchange rates and generally refers to such amounts calculated on a constant currency basis as excluding the impact of foreign exchange or being on a constant currency basis. These results should be considered in addition to, not as a substitute for, results reported in accordance with GAAP. Results on a constant currency basis, as the Company presents them, may not be comparable to similarly titled measures used by other companies and are not measures of performance presented in accordance with GAAP.
Financial Highlights
Financial Highlights
(unaudited, in thousands, except per share amounts)
Three Months Ended
March 31,
2024 2023
Total GAAP revenues $ 880,889 $ 808,673
Total GAAP operating income 91,898 24,770
Total Non-GAAP operating income 161,183 89,729
GAAP net income 169,548 21,703
Non-GAAP net income 145,269 84,577
GAAP basic EPS $ 0.76 $ 0.10
Non-GAAP basic EPS $ 0.65 $ 0.38
GAAP diluted EPS $ 0.75 $ 0.10
Non-GAAP diluted EPS $ 0.64 $ 0.37

6

Revenue Details
Revenue Details
(unaudited, in thousands)
Three Months Ended
March 31, %
Change
(as reported)
%
Change
(constant currency)1
2024 2023
Net product revenues:
Jakafi $ 571,839 $ 579,969 (1 %) (1 %)
Opzelura 85,724 56,552 52 % 51 %
Iclusig 30,343 27,685 10 % 8 %
Pemazyre 17,676 22,475 (21 %) (22 %)
Minjuvi/Monjuvi 23,874 6,556 264 % 262 %
Zynyz 467 — NM NM
Total net product revenues 729,923 693,237 5 % 5 %
Royalty revenues:
Jakavi 89,595 76,692 17 % 19 %
Olumiant 30,589 34,155 (10 %) (8 %)
Tabrecta 5,234 4,177 25 % NA
Pemazyre 548 412 33 % NM
Total royalty revenues 125,966 115,436 9 %
Total net product and royalty revenues 855,889 808,673 6 %
Milestone and contract revenues 25,000 — NM NM
Total GAAP revenues $ 880,889 $ 808,673 9 %

NM = not meaningful
NA = not available
1.Percentage change in constant currency is calculated using 2023 foreign exchange rates to recalculate 2024 results.
Product and Royalty Revenues Product revenues and product and royalty revenues for the quarter ended March 31, 2024 increased 5% and 6%, respectively, over the prior year comparative period, primarily driven by a 52% year-over-year increase in Opzelura net product revenue due to the growth in new patient starts and refills, an increase in Minjuvi/Monjuvi net product revenues, following the acquisition of the exclusive global rights to tafasitamab in February 2024, and an increase in Jakavi royalty revenues.
7

Operating Expenses
Operating Expense Summary
(unaudited, in thousands)
Three Months Ended
March 31, %
Change
2024 2023
GAAP cost of product revenues $ 60,956 $ 56,822 7 %
Non-GAAP cost of product revenues1
54,959 50,669 8 %
GAAP research and development 429,260 406,641 6 %
Non-GAAP research and development2
388,437 375,620 3 %
GAAP selling, general and administrative 300,256 315,606 (5 %)
Non-GAAP selling, general and administrative3
277,335 294,017 (6 %)
GAAP (gain) loss on change in fair value of acquisition-related contingent consideration (456) 6,196 (107 %)
Non-GAAP (gain) loss on change in fair value of acquisition-related contingent consideration4
— — — %
GAAP (profit) and loss sharing under collaboration agreements (1,025) (1,362) (25 %)

1 Non-GAAP cost of product revenues excludes the amortization of licensed intellectual property for Iclusig relating to the acquisition of the European business of ARIAD Pharmaceuticals, Inc. and the cost of stock-based compensation.
2 Non-GAAP research and development expenses exclude the cost of stock-based compensation and MorphoSys transition costs.
3 Non-GAAP selling, general and administrative expenses exclude the cost of stock-based compensation and MorphoSys transition costs.
4 Non-GAAP (gain) loss on change in fair value of acquisition-related contingent consideration is null.
Cost of product revenues GAAP and Non-GAAP cost of product revenues for the quarter ended March 31, 2024 increased 7% and 8%, respectively, compared to the same period in 2023 primarily due to growth in net product revenues.
Research and development expenses GAAP and Non-GAAP research and development expense for the quarter ended March 31, 2024 increased 6% and 3%, respectively, compared to the same period in 2023 primarily due to continued investment in our late stage development assets.
Selling, general and administrative expenses GAAP and Non-GAAP selling, general and administrative expenses for the quarter ended March 31, 2024 decreased 5% and 6%, respectively, compared to the same period in 2023 primarily due to the timing of consumer marketing activities and of certain other expenses.
Other Financial Information
Change in fair value of acquisition-related contingent consideration The change in fair value of contingent consideration during the quarter ended March 31, 2024, compared to the same periods in 2023, was due primarily to fluctuations in foreign currency exchange rates impacting future revenue projections of Iclusig.
Operating income GAAP and Non-GAAP operating income for the three months ended March 31, 2024 increased 271% and 80%, respectively, compared to the same period in 2023, driven by growth in total revenues and stable operating expenses.
Cash, cash equivalents and marketable securities position As of March 31, 2024 and December 31, 2023, cash, cash equivalents and marketable securities totaled $3.9 billion and $3.7 billion, respectively.
8

2024 Financial Guidance
Incyte is maintaining its full year 2024 revenue and expense guidance. Incyte’s guidance is summarized below. Guidance does not include revenue from any potential new product launches or the impact of the acquisition of Escient Pharmaceuticals or any other potential future strategic transactions.
Guidance
Jakafi net product revenues $2,690 – $2,750 million
Other Hematology/Oncology net product revenues(1)
$325 – $360 million
GAAP Cost of product revenues 7 – 8% of net product revenues
Non-GAAP Cost of product revenues(2)
6 – 7% of net product revenues
GAAP Research and development expenses $1,720 – $1,760 million
Non-GAAP Research and development expenses(3)
$1,580 – $1,615 million
GAAP Selling, general and administrative expenses $1,210 – $1,240 million
Non-GAAP Selling, general and administrative expenses(3)
$1,115 – $1,140 million

1Pemazyre in the U.S., EU and Japan; Monjuvi and Zynyz in the U.S.; and Iclusig and Minjuvi in the EU.
2Adjusted to exclude the amortization of licensed intellectual property for Iclusig relating to the acquisition of the European business of ARIAD Pharmaceuticals, Inc. and the estimated cost of stock-based compensation.
3 Adjusted to exclude the estimated cost of stock-based compensation.
Conference Call and Webcast Information
Incyte will hold a conference call and webcast this morning at 8:00 a.m. ET. To access the conference call, please dial 877-407-3042 for domestic callers or 201-389-0864 for international callers. When prompted, provide the conference identification number, 13745743.
If you are unable to participate, a replay of the conference call will be available for 90 days. The replay dial-in number for the United States is 877-660-6853 and the dial-in number for international callers is 201-612-7415. To access the replay you will need the conference identification number, 13745743.
The conference call will also be webcast live and can be accessed at investor.incyte.com.

On April 30, 2024 IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company advancing innovative gamma-delta T cell therapies, reported that the first patient in its Phase 2 clinical trial evaluating INB-400 in patients with newly diagnosed glioblastoma multiforme (GBM) has been successfully dosed at the Cleveland Clinic in Ohio (Press release, In8bio, APR 30, 2024, View Source [SID1234642463]).

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INB-400 is the Company’s first autologous gamma-delta T cell therapy product candidate genetically engineered to survive chemotherapy and maintain the natural ability to recognize, engage and kill cancer cells when dosed along with current, standard-of-care treatments such as temozolomide (Temodar, or TMZ). Arm A of the INB-400 trial is expected to enroll up to 40 patients. INB-400 was granted Orphan Drug Designation by the FDA in 2023.

"The initiation of patient dosing in our Phase 2 trial of INB-400 represents an important milestone for both IN8bio and patients with newly diagnosed GBM who have limited therapeutic options," said William Ho, CEO and co-founder of IN8bio. "Our novel approach combines engineered, chemotherapy-resistant gamma-delta T cells with standard-of-care treatments to potentially drive deeper responses and improved patient outcomes in difficult-to-treat cancers. We look forward to advancing INB-400 at multiple leading medical centers across the United States for patients with GBM and sharing updates, including long-term follow up data from the Phase 1 INB-200 program, at medical meetings this year."

Gamma-delta T cells are naturally occurring immune cells with unique properties enabling them to naturally differentiate between healthy and cancerous tissues. They serve to bridge between the innate and adaptive immune system, contributing to direct tumor cell killing as well as immune memory, cell recruitment and activation to drive deeper immune responses.

The Phase 2 study will evaluate the safety and tolerability of INB-400 in patients with newly diagnosed GBM in combination with TMZ. In Arm A of the trial, investigators will administer T cells to patients on the first day of each of six 28-day maintenance cycles concurrent with TMZ for up to six doses. The primary endpoint of the study is overall survival rate at 12 months. Secondary endpoints include safety and tolerability, overall response rate, time to progression, and progression-free survival.

Since 2005, the standard-of-care treatment for GBM has been surgical resection followed by radiation and chemotherapy and six cycles of maintenance temozolomide therapy, referred to as the Stupp regimen. Most patients relapse in six to seven months, with very few patients surviving beyond five years. INB-400 is engineered to be resistant to alkylating chemotherapy, enabling it to be used in combination with the current standard-of-care TMZ to amplify immune signals, maximize tumor killing, and eliminate cancer cells.

More information about the Phase 2 study (NCT05664243) can be found at www.clinicaltrials.gov.

About INB-400

INB-400 is IN8bio’s DeltEx chemotherapy resistant autologous drug-resistant immunotherapy (DRI). INB-400 was granted Orphan Drug Designation for the treatment of glioblastoma multiforme (GBM) by the FDA in April 2023, marking the first genetically modified gamma-delta T cell therapy to receive this regulatory designation. GBM remains a significant unmet need, treatment options and associated outcomes for GBM, highly aggressive and difficult-to-treat brain cancer, have remained largely unchanged for more than 18 years, with a median progression free survival of 6-7 months and overall survival of 14-16 months. Allogeneic INB-400 will expand the application of DRI gamma-delta T cells into other solid tumor types through the development of allogeneic or "off-the-shelf" DeltEx DRI.