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This discussion and analysis should be read in conjunction with our financial statements and the accompanying notes included in this report and the audited financial statements and accompanying notes included in our Annual Report on Form 10-K for the year ended December 31, 2023 filed with the SEC on March 5, 2024.
−Removed: Our financial results for the three months ended March 31, 2024 are not necessarily indicative of results that may occur in future interim periods or for the full fiscal year.
+Added: Our financial results for the three and six months ended June 30, 2024 are not necessarily indicative of results that may occur in future interim periods or for the full fiscal year.
This Quarterly Report on Form 10-Q contains statements indicating expectations about future performance and other forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (Securities Act) and Section 21E of the Securities Exchange Act of 1934, as amended (Exchange Act), and the Private Securities Litigation Reform Act of 1995, that involve risks and uncertainties.
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We focus on products that address signaling pathways that are critical to disease mechanisms.
−Removed: Our first product approved by the FDA is TAVALISSE (fostamatinib disodium hexahydrate) tablets, the only approved oral SYK inhibitor for the treatment of adult patients with chronic ITP who have had an insufficient response to a previous treatment.
+Added: TAVALISSE (fostamatinib disodium hexahydrate) is our first product approved by the FDA.
+Added: TAVALISSE is the only approved oral SYK inhibitor for the treatment of adult patients with chronic ITP who have had an insufficient response to a previous treatment.
The product is also commercially available in Europe and the UK (as TAVLESSE), and in Canada, Israel and Japan (as TAVALISSE) for the treatment of chronic ITP in adult patients.
−Removed: Our second FDA-approved product is REZLIDHIA (olutasidenib) capsules for the treatment of adult patients with R/R AML with a susceptible IDH1 mutation as detected by an FDA-approved test.
−Removed: We began our commercialization of REZLIDHIA in December 2022.
−Removed: W e in-licensed olutasidenib from Forma, with exclusive, worldwide rights for its development, manufacturing and commercialization.
−Removed: In February 2024, we entered into an Asset Purchase Agreement with Blueprint to purchase certain assets comprising the right to research, develop, manufacture and commercialize GAVRETO (pralsetinib) in the US.
−Removed: GAVRETO (pralsetinib) is a once daily, small molecule, oral, kinase inhibitor of wild-type RET and oncogenic RET fusions.
+Added: REZLIDHIA (olutasidenib) is o ur second FDA-approved product.
+Added: REZLIDHIA capsules are indicated for the treatment of adult patients with R/R AML with a susceptible IDH1 mutation as detected by an FDA-approved test.
+Added: W e in-licensed REZLIDHIA from Forma with exclusive, worldwide rights for its development, manufacturing and commercialization.
+Added: GAVRETO (pralsetinib) is our third FDA-approved product which we began commercializing on June 27, 2024.
+Added: GAVRETO is a once daily, small molecule, oral, kinase inhibitor of wild-type RET and oncogenic RET fusions.
GAVRETO is approved by the FDA for the treatment of adult patients with metastatic RET fusion-positive NSCLC as detected by an FDA-approved test.
GAVRETO is also approved under accelerated approval based on overall response rate and duration response rate, for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).
−Removed: We intend to distribute and market GAVRETO for approved indications in RET fusion-positive NSCLC and advanced thyroid cancers, and we expect to complete the transition of the asset and start recognizing product sales in July of 2024.
−Removed: We continue to advance the development of our IRAK1/4 inhibitor program, in an open-label, Phase 1b trial to determine the tolerability and preliminary efficacy of the drug in patients with lower-risk MDS who are refractory or resistant to prior therapies.
−Removed: We have strategic development collaborations with MDACC to expand our evaluation of REZLIDHIA (olutasidenib) in AML and other hematologic cancers, and with CONNECT to conduct a Phase 2 clinical trial to evaluate REZLIDHIA (olutasidenib) in combination with temozolomide in patients with HGG harboring an IDH1 mutation.
+Added: We acquired the rights to research, develop, manufacture and commercialize GAVRETO in the US from Blueprint pursuant to an Asset Purchase Agreement entered in February 2024.
+Added: We continue to advance the development of R289, our IRAK 1/4 inhibitor program, in an open-label, Phase 1b trial to determine the tolerability and preliminary efficacy of the drug in patients with lower-risk MDS who are relapsed, refractory or resistant to prior therapies.
+Added: We have strategic development collaborations with MDACC to expand our evaluation of REZLIDHIA in AML and other hematologic cancers with IDH1 mutations, and with CONNECT to conduct a Phase 2 clinical trial to evaluate REZLIDHIA in combination with temozolomide in patients with HGG harboring an IDH1 mutation.
We have a RIPK1 inhibitor program in clinical development with our partner Lilly.
We also have product candidates in clinical development with partners BerGenBio and Daiichi.
+Added: Reverse Stock Split
+Added: We filed with the Secretary of State of the State of Delaware a certificate of amendment to our Amended and Restated Certificate of Incorporation, to effect a 1-for-10 reverse stock split, effective June 27, 2024.
+Added: As a result of the reverse stock split, every ten issued and outstanding shares of our common stock were automatically combined into one issued and outstanding share of common stock.
+Added: Accordingly, an amount equal to the par value of the decreased shares resulting from the reverse stock split was reclassified from common stock to additional paid-in capital on the condensed balance sheet and statement of changes in stockholders’ deficit.
+Added: No fractional shares were issued in connection with the reverse stock split.
+Added: Stockholders who otherwise would be entitled to receive fractional shares of common stock were entitled to receive the cash value equal to the fraction to which the stockholder would otherwise be entitled, multiplied by the closing price of the common stock as reported by Nasdaq on the last trading day prior to the effective date of the split.
+Added: As a result of the reverse stock split, proportionate adjustments were made to the number of shares underlying (and as applicable, the exercise or conversion prices of) our outstanding equity awards and to the number of shares of common stock issuable under our equity incentive plans.
+Added: The reverse stock split did not change the par value of our common stock, which remains $0.001, or the authorized number of shares of our common stock.
+Added: All share amounts and per share amounts disclosed in this Quarterly Report on Form 10-Q have been adjusted to reflect the reverse stock split on a retroactive basis for all periods presented.
Business Updates
TAVALISSE IN ITP
−Removed: For the three months ended March 31, 2024, net product sales of TAVALISSE were $21.1 million, decreased by $1.2 million or 5% compared to $22.3 million net product sales in the same period in 2023.
−Removed: The decrease was driven partly by a decrease in number of bottles remaining in distributors channels, and partly due to the increase in revenue reserves driven by higher government and private payor rebates.
−Removed: These decreases were partially offset by the increase in price per bottle of TAVALISSE.
−Removed: Typically, our first quarter net sales are impacted by the first quarter reimbursement issues such as the resetting of co-pays and the Medicare donut hole.
+Added: For the six months ended June 30, 2024, net product sales of TAVALISSE were $47.5 million, increased by $3.8 million or 9% compared to $43.6 million net product sales in the same period in 2023.
+Added: The increase was primarily due to increased quantities sold, as well as increased price per bottle.
+Added: This increase was partially offset by the increase in revenue reserves driven by higher government and private payor rebates.
REZLIDHIA in R/R AML with mIDHI
−Removed: For the three months ended March 31, 2024, net product sales of REZLIDHIA were $4.9 million, increased by $3.4 million compared to $1.5 million net product sales in the same period in 2023.
+Added: For the six months ended June 30, 2024, net product sales of REZLIDHIA were $10.0 million, increased by $6.0 million or 150% compared to $4.0 million net product sales in the same period in 2023.
The increase was primarily due to increased quantities sold primarily driven by increased number of patients under therapy, partially offset by the increase in revenue reserves primarily due to higher government rebates.
−Removed: W e in-licensed olutasidenib from Forma, with exclusive, worldwide rights for development, manufacturing and commercialization of olutasidenib for any uses, including for the treatment of AML and other malignancies.
−Removed: In accordance with the terms of the license and transition services agreement, we paid an upfront fee of $2.0 million, with the potential to pay up to $67.5 million additional payments upon achievement of specified development and regulatory milestones and up to $165.5 million additional payments upon achievement of certain commercial milestones.
−Removed: In addition, subject to the terms and conditions of the license and transition services agreement, Forma would be entitled to tiered royalty payments on net sales of licensed products at percentages ranging from low-teens to mid-thirties, as well as certain portions of our sublicensing revenue, subject to certain standard reductions and offsets.
−Removed: In 2022, certain milestones were met which entitled Forma to receive a $17.5 million milestone payments.
−Removed: No new milestone was met in 2023 and during the three months ended March 31, 2024.
−Removed: GAVRETO (pralsetinib) in metastatic RET fusion-positive NSCLC and advanced thyroid cancers
−Removed: On February 22, 2024, we entered into an Asset Purchase Agreement with Blueprint to purchase certain assets comprising the right to research, develop, manufacture and commercialize GAVRETO (pralsetinib) in the US.
−Removed: Under the terms of the agreement, we agreed to pay Blueprint a purchase price of $15.0 million, $10.0 million of which is payable upon our first commercial sale of GAVRETO (pralsetinib) and an additional $5.0 million of which is payable on the first anniversary of the closing date of the agreement, subject to certain conditions.
+Added: GAVRETO in metastatic RET fusion-positive NSCLC and advanced thyroid cancers
+Added: We began our commercialization and started recognizing revenue from product sales of GAVRETO in June 2024.
+Added: We recognized approximately $1.9 million of net product sales for the sale of GAVRETO to our distributors at the end of June 2024.
+Added: We believe GAVRETO is highly synergistic with our current product portfolio, and we expect to continue to leverage our existing commercial infrastructure to ensure current and newly prescribed GAVRETO patients have continued access to this important treatment option.
+Added: We distribute and market GAVRETO for approved indications in RET fusion-positive NSCLC and advanced thyroid cancers.
+Added: We acquired GAVRETO from Blueprint pursuant to an Asset Purchase Agreement entered into on February 22, 2024.
+Added: Pursuant to the Asset Purchase Agreement, we purchased certain assets comprising the right to research, develop, manufacture and commercialize GAVRETO in the US from Blueprint.
+Added: Under the terms of the agreement, we agreed to pay Blueprint a purchase price of $15.0 million, of which, $10.0 million was paid in July 2024 following our first commercial sale of GAVRETO at the end of June 2024, and an additional $5.0 million is payable on the first anniversary of the closing date of the agreement, subject to certain conditions.
Blueprint is also eligible to receive up to $97.5 million in future commercial milestone payments and up to $5.0 million in future regulatory milestone payments, in addition to tiered royalties ranging from 10% to 30%.
−Removed: Simultaneously and in conjunction with entering into the Asset Purchase Agreement, we also entered into certain supporting agreements, including a customary transition agreement, pursuant to which, during the transition period, Blueprint will transition regulatory and distribution responsibility for GAVRETO (pralsetinib) to us.
−Removed: We also agreed to purchase certain drug product inventories from Blueprint amounting to approximately $7.0 million under a Material Transfer Agreement.
−Removed: As of March 31, 2024, we received inventories amounting to approximately $3.1 million, and the remaining inventories are expected to be delivered to us in the second quarter of 2024.
−Removed: We believe GAVRETO will be highly synergistic with our current product portfolio, and we expect to leverage our existing commercial infrastructure to ensure current and newly prescribed GAVRETO patients have continued access to this important treatment option.
−Removed: We intend to distribute and market GAVRETO for approved indications in RET fusion-positive NSCLC and advanced thyroid cancers, and we expect to complete the transition of the asset and start recognizing product sales in July of 2024.
−Removed: GAVRETO (pralsetinib) is a once daily, small molecule, oral, kinase inhibitor of wild-type RET and oncogenic RET fusions.
−Removed: Currently, GAVRETO (pralsetinib) is one of only two approved RET inhibitors on the market for patients.
−Removed: GAVRETO is approved by the FDA for the treatment of adult patients with metastatic RET fusion-positive NSCLC as detected by an FDA-approved test.
−Removed: GAVRETO is also approved for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).
−Removed: This indication was approved by the FDA under accelerated approval based on overall response rate and duration of response.
−Removed: Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial.
−Removed: Discussions with the FDA regarding confirmatory requirements are ongoing.
−Removed: GAVRETO has been co-marketed by Blueprint and Genentech, a member of Roche Group (Roche), to patients in the US since September 2020 pursuant to a collaboration agreement between Blueprint and Roche, which was terminated effective in February 2024.
−Removed: The patent portfolio covering pralsetinib contains patents and patent applications directed to compositions of matter for pralsetinib, including solid forms, formulations, and methods of use and manufacture.
−Removed: Pralsitenib is covered as a composition of matter in a US issued patent that has an expiration date in November 2036 and subject to potential extensions.
−Removed: Patents that have been issued or are expected to be issued covering pralsetinib will have statutory expiration dates between 2036 and 2041.
−Removed: Patent term adjustments, patent term extensions, and supplementary protection certificates could result in later expiration dates.
−Removed: The FDA granted GAVRETO (pralsetinib) new chemical entity exclusivity until September 2025 and orphan drug exclusivity until September 2027 with respect to the approval for treatment of adult
−Removed: patients with metastatic RET fusion-positive NSCLC as detected by an FDA-approved test.
−Removed: The FDA also granted GAVRETO (pralsetinib) two orphan drug exclusivities until December 2027 with respect to FDA approval for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate), and for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid carcinoma who require systemic therapy.
−Removed: RET is involved in the physiological development of some organ systems.
−Removed: RET is a receptor tyrosine kinase that activates multiple downstream pathways involved in cell proliferation and survival.
−Removed: RET can be activated by mutation or when a portion of the RET gene that encodes the kinase domain is joined to part of another gene creating a fusion gene that encodes an aberrantly activated RET fusion protein.
−Removed: RET alterations, such as fusions or mutations, drive the growth of multiple tumor types.
−Removed: It is estimated that over 230,000 adult patients in the US will be diagnosed with lung cancer in 2024.
−Removed: NSCLC is the most common type of lung cancer in the US accounting for 80-85% of all lung cancer diagnoses.
−Removed: RET activating fusions are key disease drivers in NSCLC.
−Removed: RET fusions are implicated in approximately 1-2% of patents with NSCLC.
−Removed: GAVRETO (pralsetinib) faces competition for RET fusion-positive NSCLC and advanced thyroid cancers from Lilly’s selpercatinib.
−Removed: In addition, other commercially available therapies used to treat RET fusion-positive NSCLC include cabozantanib and platinum-based chemotherapy regimens with or without pembrolizumab, atezolizumab, nivolumab/ipilumumab, cemiplimab or tremelimumab-durvalumab.
−Removed: Pralsetinib may also face competition from other drug candidates in development for RET-altered cancers, as well as multi-kinase inhibitors with RET activity being evaluated in clinical trials.
−Removed: R289, an Oral IRAK1/4 Inhibitor for Hematology-Oncology, Autoimmune, and Inflammatory Diseases
+Added: Simultaneously and in conjunction with entering into the Asset Purchase Agreement, we also entered into certain supporting agreements, including a customary transition agreement, pursuant to which, during the transition period, Blueprint will transition regulatory and distribution responsibility for GAVRETO to us.
+Added: We also agreed to purchase certain drug product inventories from Blueprint under a Material Transfer Agreement, and received such inventories amounting to approximately $6.5 million during the six months ended June 30, 2024.
+Added: R289, an Oral IRAK1/4 Inhibitor for LR-MDS
We advanced the development of our IRAK 1/4 inhibitor program, following further evaluation of single and multiple ascending doses of R289 in healthy subjects.
−Removed: The Phase 1b open-label, multicentrial trial evaluates the safety, tolerability and preliminary efficacy of R289 in patients with R/R lower-risk MDS.
+Added: The Phase 1b open-label, multicenter trial evaluates the safety, tolerability and preliminary efficacy of R289 in patients with R/R lower-risk MDS.
This Phase 1b trial is expected to enroll approximately 40 patients (up to 30 participants in the dose escalation phase, and up to 10 participants in the dose expansion phase).
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The safety and efficacy data from this Phase 1b trial is intended to inform the recommended dose of R289 for further clinical evaluation in lower-risk MDS.
−Removed: To date, enrollment in the third cohort of the trial has been completed and we are planning to include two additional cohorts with twice daily dosing regimens.
+Added: To date, enrollment in the fourth dose level (250 mg twice daily) of the trial is underway.
Preliminary data are expected by the end of 2024.
−Removed: REZLIDHIA (olutasidenib) in AML, Other Hematologic Cancers and HGG
+Added: REZLIDHIA in AML, Other Hematologic Cancers and HGG
In December 2023, we entered into a Strategic Collaboration Agreement with MDACC, a comprehensive cancer research, treatment, and prevention center.
−Removed: The collaboration will expand our evaluation of REZLIDHIA (olutasidenib) in AML and other hematologic cancers with IDH1 mutations.
+Added: The collaboration will expand our evaluation of REZLIDHIA in AML and other hematologic cancers with IDH1 mutations.
Under the Strategic Collaboration Agreement, we will jointly lead the clinical development efforts with MDACC to evaluate the potential of olutasidenib to treat newly diagnosed and R/R patients with AML, higher-risk MDS, and advanced myeloproliferative neoplasms, in combination with other agents.
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Under the Strategic Collaboration Agreement, we will provide MDACC the study materials and $15.0 million in time-based milestone payments as compensation for services to be provided for the studies, over the five-year collaboration term, unless terminated earlier as provided for in the agreement.
−Removed: Through March 31, 2024, we provided $2.0 million funding to MDACC.
−Removed: In January 2024, we announced our collaboration with Collaborative Network for Neuro-Oncology Clinical Trials (CONNECT), an international collaborative network of pediatric cancer centers, to conduct a Phase 2 clinical trial to evaluate REZLIDHIA (olutasidenib) in combination with temozolomide in patients with HGG harboring an IDH1 mutation.
+Added: Through June 30, 2024, we provided $2.0 million funding to MDACC.
+Added: In early August 2024, MDACC, with our support, opened enrollment for a Phase 1b/2 trial of decitabine and venetoclax in combination with olutasidenib in patients with IDH1-mutated AML.
+Added: This is the first trial in our multi-year strategic development collaboration with MDACC.
+Added: The Phase 1b part of the trial seeks to determine the safety and tolerability and recommended Phase 2 dose of decitabine and venetoclax in combination with olutasidenib.
+Added: The primary objective of the Phase 2 part of the trial is to determine the complete remission rate in both newly diagnosed and R/R patients.
+Added: In January 2024, we announced our collaboration with Collaborative Network for Neuro-Oncology Clinical Trials (CONNECT), an international collaborative network of pediatric cancer centers, to conduct a Phase 2 clinical trial to evaluate REZLIDHIA in combination with temozolomide in patients with HGG harboring an IDH1 mutation.
Under the collaboration, CONNECT will include olutasidenib in CONNECT’s TarGet-D, a molecularly guided Phase 2 umbrella clinical trial for HGG.
−Removed: Our sponsored arm, adolescents and young adult patients (<39 years old) with newly-diagnosed IDH1-mutation positive HGG will receive maintenance therapy with of olutasidenib in combination with temozolomide for the first year after radiotherapy, followed by olutasidenib monotherapy for the second year.
+Added: In our sponsored arm, adolescents and young adult patients (<39 years old) with newly-diagnosed IDH1-mutation positive HGG will receive maintenance therapy with of olutasidenib in combination with temozolomide for the first year after radiotherapy, followed by olutasidenib monotherapy for the second year.
Under the collaboration, we will provide CONNECT with a funding up to $3.0 million and study material over the four-year collaboration.
Global Strategic Partnership with Lilly
−Removed: Lilly is continuing to advance R552, an investigational, potent and selective RIPK1 inhibitor.
−Removed: Lilly has initiated the Phase 2a trial studying R552 in adult patients with moderately to severely active rheumatoid arthritis.
−Removed: The trial plans to enroll 100 patients globally.
+Added: Lilly is continuing to advance ocadusertib (previously R552), an investigational, potent and selective RIPK1 inhibitor.
+Added: Lilly has initiated the Phase 2a trial studying ocadusertib in adult patients with moderately to severely active rheumatoid arthritis.
+Added: The Phase 2a enrollment of approximately 100 patients is advancing well, with preliminary analysis of the Phase 2a results anticipated in the first half of 2025.
RIPK1 is implicated in a broad range of key inflammatory cellular processes and plays a key role in tumor necrosis factor signaling, especially in the induction of pro-inflammatory necroptosis.
The program also includes RIPK1 compounds that cross the blood-brain barrier (CNS-penetrants) to address neurodegenerative diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis.
−Removed: Under the Lilly Agreement, we are responsible for 20% of the development costs for R552 in the US, Europe, and Japan, up to a specified cap.
−Removed: Lilly is responsible for funding the remainder of all development activities for R552 and other non-CNS disease development candidates.
−Removed: Under the Lilly Agreement, we have the right to opt-out of co-funding the R552 development activities in the US, Europe and Japan at two different specified times and as a result receive lesser royalties from sales.
−Removed: Prior to us providing our first opt-out notice as discussed below, we were required to fund our share of the R552 development activities in the US, Europe, and Japan up to a maximum funding commitment of $65.0 million through April 1, 2024.
−Removed: On September 28, 2023, we entered into an amendment to the Lilly Agreement which provides, among other things, that if we exercise our first opt-out right, we have the right to opt-in to co-funding of R552 development, upon us providing notice to Lilly within 30 days of certain events, as specified in the Lilly Agreement.
−Removed: Following the amendment to the Lilly Agreement, in September 2023, we provided the first opt-out notice to Lilly.
−Removed: We continue to fund our share of the R552 development activities up to $22.6 million through April 1, 2024 as provided for in the amended Lilly Agreement.
−Removed: Through March 31, 2024, Lilly billed us $20.3 million of the funding development costs incurred as of the fourth quarter of 2023.
+Added: Under the Lilly Agreement, we are responsible for 20% of the development costs for ocadusertib in the US, Europe, and Japan, up to a specified cap, and Lilly is responsible for funding the remainder of all development activities for ocadusertib and other non-CNS disease development candidates.
+Added: Under the Lilly Agreement, we have the right to opt-out of co-funding the ocadusertib development activities in the US, Europe and Japan at two different specified times and as a result receive lesser royalties from sales.
+Added: In September 2023, we provided the first opt-out notice to Lilly and our funding commitment was capped at a specified amount through April 1, 2024, as provided for in the Lilly Agreement, as amended in September 2023 .
+Added: We provided $21.4 million funding to Lilly throughout the periods for our share for ocadusertib development costs incurred through April 1, 2024.
+Added: Under the Lilly Agreement as amended, we have the right to opt-in to co-funding of ocadusertib development, upon us providing notice to Lilly within 30 days of certain events, as specified in the Lilly Agreement.
If we decide to exercise our opt-in right, we will be required to continue to share in global development costs, and if we later exercise our second opt-out right (no later than April 1, 2025), our share in global development costs will be up to a specified cap through December 31, 2025, as provided for in the Lilly Agreement.
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The results of our Phase 2 clinical trial, in which fostamatinib was orally administered to 16 adults with chronic ITP, published in Blood , showed that fostamatinib significantly increased the platelet counts of certain ITP patients, including those who had failed other currently available agents.
−Removed: Our Fostamatinib for Immune Thrombocytopenia (FIT) Phase 3 clinical program had a total of 150 ITP patients which were randomized into two identical multi-center, double-blind, placebo-controlled clinical trials.
+Added: Our Fostamatinib for Immune Thrombocytopenia (FIT) Phase 3 clinical program had a total of 150 ITP patients which were randomized into two identical multicenter, double-blind, placebo-controlled clinical trials.
The patients were diagnosed with persistent or chronic ITP, and had blood platelet counts consistently below 30,000 per microliter of blood.
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In October 2016, we announced the results of the second FIT study, reporting that the response rate (16% in the treatment group, versus 4% in the placebo group) was consistent with the first study, although the difference was not statistically significant.
−Removed: In the ITP double-blind studies, the most commonly reported adverse reactions occurring in at least 5% of patients treated with TAVALISSE were diarrhea, hypertension, nausea, dizziness, increased alanine aminotransferase, increased aspartate
−Removed: aminotransferase, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.
+Added: In the ITP double-blind studies, the most commonly reported adverse reactions occurring in at least 5% of patients treated with TAVALISSE were diarrhea, hypertension, nausea, dizziness, increased alanine aminotransferase, increased aspartate aminotransferase, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.
Serious adverse drug reactions occurring in at least 1% of patients treated with TAVALISSE in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis.
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TAVALISSE was approved by the FDA in April 2018 for the treatment of ITP in adult patients who have had an insufficient response to a previous treatment, and successfully launched in the US in May 2018.
−Removed: In January 2020, the European Commission (EC) granted a centralized MA for fostamatinib (TAVLESSE) valid throughout the European Union (EU) and in the UK, after the departure of the UK from the EU, for the treatment of chronic ITP in adult patients who are refractory to other treatments.
−Removed: In December 2022, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) approved the NDA for fostamatinib in chronic ITP.
Competitive landscape for TAVALISSE
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Other products in the US that are approved by the FDA to increase platelet production through binding to TPO receptors on megakaryocyte precursors include PROMACTA ® (Novartis International AG (Novartis)), Nplate ® (Amgen, Inc.) and DOPTELET ® (Swedish Orphan Biovitrum AB).
−Removed: In the longer term, we may eventually face competition from potential manufacturers of generic versions of our marketed products, including the proposed generic version of TAVALISSE that is the subject of an ANDA submitted to the FDA by Annora, which, if approved and allowed to enter the market, it could result in significant decreases in the revenue derived from sale of TAVALISSE and thereby materially harm our business and financial condition.
+Added: In the longer term, we may eventually face competition from
+Added: potential manufacturers of generic versions of our marketed products, including the proposed generic version of TAVALISSE that is the subject of an ANDA submitted to the FDA by Annora, which, if approved and allowed to enter the market, it could result in significant decreases in the revenue derived from sale of TAVALISSE and thereby materially harm our business and financial condition.
Commercial activities, including sales and marketing
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We have a fully integrated commercial team consisting of sales, marketing, market access, and commercial operations functions.
−Removed: Our sales team promotes our products in the US using customary
−Removed: pharmaceutical company practices, and we concentrate our efforts on hematologists and hematologist-oncologists.
+Added: Our sales team promotes our products in the US using customary pharmaceutical company practices.
Our products are sold initially through third-party wholesale distribution and specialty pharmacy channels and group purchasing organizations before being ultimately prescribed to patients.
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We believe that our commercial team and distribution practices are adequate to ensure that our marketing efforts reach relevant customers and deliver our products to patients in a timely and compliant fashion.
−Removed: Also, to help ensure that all eligible patients in the US have appropriate access to our products, we have established a reimbursement and patient support program called Rigel OneCare (ROC).
+Added: Also, to help ensure that all eligible patients in the US have appropriate access to our products, we have established a reimbursement and patient support program called Rigel OneCare TM (ROC).
Through ROC, we provide co-pay assistance to qualified, commercially insured patients to help minimize out-of-pocket costs and provide free product to uninsured or under-insured patients who meet certain established clinical and financial eligibility criteria.
In addition, ROC is designed to provide reimbursement support, such as information related to prior authorizations, benefits investigations and appeals.
−Removed: We have entered into various license and commercial agreements to commercialize fostamatinib globally, but we retain the global rights to fostamatinib outside of the respective territories under such license and commercial agreements.
−Removed: Our collaborative partner Grifols S.A.
−Removed: (Grifols) launched TAVLESSE in the UK and certain countries in Europe including Germany, France, Italy and Spain, and continues a phased rollout across the rest of Europe.
−Removed: Our collaborative partner Medison Pharma Trading AG (Medison Canada) and Medison Pharma Ltd.
−Removed: (Medison Israel, and together with Medison Canada, Medison) launched TAVALISSE in Canada and Israel.
−Removed: Further, our collaborative partner Kissei Pharmaceutical Co., Ltd.
−Removed: (Kissei) launched TAVALISSE in Japan.
−Removed: Fostamatinib in Europe
−Removed: We have a commercialization license agreement with Grifols entered in January 2019, for exclusive rights to commercialize fostamatinib for human diseases, and non-exclusive rights to develop, fostamatinib in their territory.
−Removed: Grifols territory includes Europe, the UK, Turkey, the Middle East, North Africa and Russia (including Commonwealth of Independent States).
−Removed: Under the terms of the agreement, we received an upfront cash payment of $30.0 million and will be eligible to receive regulatory and commercial milestones of up to $297.5 million.
−Removed: In January 2020, the EC granted a MA for fostamatinib for the treatment of chronic ITP in adult patients who are refractory to other treatments.
−Removed: With this approval, we received a $20.0 million non-refundable milestone payment, consisted of a $17.5 million payment due upon Market Authorization Application (MAA) approval by the EMA of fostamatinib for the first indication and a $2.5 million creditable advance royalty payment due upon EMA approval of fostamatinib in the first indication.
−Removed: We are also entitled to receive stepped double-digit royalty payments based on tiered net sales which may reach 30% of net sales of fostamatinib in the Grifols territory.
+Added: We have entered into various license and commercial agreements to commercialize fostamatinib globally as discussed below, but we retain the global rights to fostamatinib outside of the respective territories under such license and commercial agreements.
+Added: Fostamatinib in EU and in the UK
+Added: We have a commercialization license agreement with Grifols S.A.
+Added: (Grifols) entered in January 2019, for exclusive rights to commercialize fostamatinib for human diseases, and non-exclusive rights to develop, fostamatinib in their territory.
+Added: Grifols territory includes EU, the UK, Turkey, the Middle East, North Africa and Russia (including Commonwealth of Independent States).
+Added: In January 2020, the European Commission (EC) granted a centralized MA for fostamatinib (TAVLESSE) valid throughout the Europe and in the UK, after the departure of the UK from the EU, for the treatment of chronic ITP in adult patients who are refractory to other treatments.
+Added: Grifols has launched TAVLESSE in the UK and certain countries in EU including Germany, France, Italy and Spain, and continues a phased rollout across the rest of EU.
Fostamatinib in Asia
−Removed: We have an exclusive license and supply agreement with Kissei entered in October 2018, to develop and commercialize fostamatinib in all current and potential indications in Kissei’s territory, which includes Japan, China, Taiwan and the Republic of Korea.
+Added: We have an exclusive license and supply agreement with Kissei Pharmaceutical Co., Ltd.
+Added: (Kissei) entered in October 2018, to develop and commercialize fostamatinib in all current and potential indications in Kissei’s territory, which includes Japan, China, Taiwan and the Republic of Korea.
Kissei is a Japan-based pharmaceutical company addressing patients’ unmet medical needs through its research, development and commercialization efforts, as well as through collaborations with partners.
−Removed: Under the terms of the agreement, we received an upfront cash payment of $33.0 million, with the potential for an additional $147.0 million in development and commercial milestone payments, and will receive product transfer price payments in the mid to upper twenty percent range based on tiered net sales for the exclusive supply of fostamatinib.
−Removed: Kissei receives exclusive rights to fostamatinib in ITP and all future indications in Kissei’s territory.
−Removed: In September 2019, Kissei initiated a Phase 3 trial in Japan of fostamatinib in adult Japanese patients with chronic ITP.
−Removed: The efficacy and safety of orally administered fostamatinib was assessed by comparing it with placebo in a randomized, double-blind study.
Japan has the third highest prevalence of chronic ITP in the world behind the US and Europe.
−Removed: In February 2020, Kissei was granted orphan drug designation from the Japanese Ministry of Health, Labor and Welfare for R788 (fostamatinib) in chronic ITP.
−Removed: In December 2021, Kissei reported positive top-line results for a Phase 3 clinical trial, meeting its primary endpoint.
−Removed: The Phase 3 clinical trial showed that patients receiving fostamatinib achieved a stable platelet response significantly higher than patients receiving a placebo control.
−Removed: Based on the positive
−Removed: Phase 3 results, in April 2022, Kissei submitted an NDA to Japan’s PMDA for fostamatinib in chronic ITP.
−Removed: With this milestone event, we received $5.0 million non-refundable and non-creditable payment from Kissei.
−Removed: In December 2022, Japan’s PMDA approved TAVALISSE for the treatment of chronic ITP.
−Removed: With this milestone event, we received $20.0 million non-refundable and non-creditable payment from Kissei based on the terms of our collaboration agreement.
−Removed: In April 2023, Kissei launched TAVALISSE for chronic ITP in Japan.
+Added: Kissei was granted orphan drug designation from the Japanese Ministry of Health, Labor and Welfare for R788 (fostamatinib) in chronic ITP in February 2020.
+Added: Kissei initiated a Phase 3 trial in Japan of fostamatinib in adult Japanese patients with chronic ITP in September 2019, and reported positive top-line results meeting its primary end point in December 2021.
+Added: The efficacy and safety of orally administered fostamatinib was assessed by comparing it with placebo in a randomized, double-blind study.
+Added: The trial showed that patients receiving fostamatinib achieved a stable platelet response significantly higher than patients receiving a placebo control.
+Added: Based on the positive Phase 3 results, Kissei submitted an NDA to Japan’s PMDA for fostamatinib in chronic ITP in April 2022.
+Added: In December 2022, Japan’s PMDA approved TAVALISSE for the treatment of chronic ITP, and in April 2023, Kissei launched TAVALISSE for chronic ITP in Japan.
Fostamatinib in Canada/Israel
−Removed: We have two exclusive commercial and license agreements with Medison entered in October 2019, to commercialize fostamatinib in all potential indications in Canada and Israel.
−Removed: Under the terms of the agreements, we received an upfront payment of $5.0 million with the potential for approximately $35.0 million in regulatory and commercial milestones.
−Removed: In addition, we will receive royalty payments beginning at 30% of net sales.
−Removed: Under our agreement with Medison for the Canada territory, we have the option to buy back all rights to the product upon regulatory approval in Canada for the indication of AIHA.
−Removed: The buyback provision, if exercised, would require both parties to mutually agree on commercially reasonable terms for us to purchase back the rights, taking into account Medison’s investment and the value of the rights, among others.
+Added: We have two exclusive commercial and license agreements with Medison Pharma Trading AG (Medison Canada) and Medison Pharma Ltd.
+Added: (Medison Israel, and together with Medison Canada, Medison) entered in October 2019, to commercialize fostamatinib in all potential indications in Canada and Israel.
Pursuant to this exclusive commercialization license agreement, in August 2020, we entered into a commercial supply agreement with Medison.
In November 2020, Health Canada approved the New Drug Submission for TAVALISSE for the treatment of thrombocytopenia in adult patients with chronic ITP who have had an insufficient response to other treatments.
−Removed: In August 2021, Medison Israel received the licenses for registrational approval from the Ministry of Health, which event entitled us to receive $0.1 million of non-refundable milestone payment.
−Removed: In November 2022, Medison Israel made its first commercial sale of TAVALISSE and obtained its national reimbursement in February 2023.
+Added: In August 2021, Medison Israel received the licenses for registrational approval from the Ministry of Health.
+Added: Medison launched TAVALISSE in Canada and Israel.
Fostamatinib in Latin America
−Removed: In May 2022, we entered into commercial license agreement with Knight Therapeutics International SA ( Knight) for the commercialization of fostamatinib for approved indications in Latin America, consisting of Mexico, Central and South America, and the Caribbean (Knight territory).
−Removed: Pursuant to such commercial license agreement, we received a $2.0 million one-time, non-refundable, and non-creditable upfront payment, with potential for up to an additional $20.0 million in regulatory and sales-based commercial milestone payments, and will receive twenty- to mid-thirty percent, tiered, escalated net-sales based royalty payments for products sold in the Knight territory.
+Added: We have a commercial license agreement with Knight Therapeutics International SA ( Knight) entered in May 2022, to commercialize fostamatinib for approved indications in Latin America, consisting of Mexico, Central and South America, and the Caribbean (Knight territory).
We are also responsible for the exclusive manufacture and supply of fostamatinib for all future development and commercialization activities under a Commercial and Supply Agreement.
9 unchanged sentences
Olutasidenib was designated by the FDA as an orphan drug for the treatment of AML, which provides orphan drug market exclusivity from the time of marketing approval on December 1, 2022.
−Removed: REZLIDHIA (olutasidenib) is designed to bind to and inhibit mIDH1 to reduce 2-hydroxyglutarate levels and restore normal cellular differentiation of myeloid cells.
+Added: REZLIDHIA is designed to bind to and inhibit mIDH1 to reduce 2-hydroxyglutarate levels and restore normal cellular differentiation of myeloid cells.
REZLIDHIA is a novel, non-intensive monotherapy treatment in the R/R AML setting demonstrating a CR+CRh rate of 35% in patients with over 90% of those responders in complete remission.
−Removed: On December 1, 2022, the FDA has approved REZLIDHIA capsules for the treatment of adult patients with R/R AML with IDH1 mutation as detected by an FDA-approved test.
−Removed: On December 22, 2022, we began the commercialization of REZLIDHIA and made it available to patients.
+Added: W e in-licensed REZLIDHIA from Forma pursuant to a license and transition services agreement entered in July 2022, with exclusive, worldwide rights for development, manufacturing and commercialization of REZLIDHIA for any uses, including for the treatment of AML and other malignancies.
+Added: In accordance with the terms of the license and transition services agreement, we paid an upfront fee of $2.0 million, with the potential to pay up to $67.5 million additional payments upon achievement of specified development and regulatory milestones and up to $165.5 million additional payments upon achievement of certain commercial milestones.
+Added: In addition, subject to the terms and conditions of the license and transition services agreement, Forma would be entitled to tiered royalty payments on net sales of licensed products at percentages ranging from low-teens to mid-thirties, as well as certain portions of our sublicensing revenue, subject to certain standard reductions and offsets.
+Added: In 2022, certain milestones were met which entitled Forma to receive a $17.5 million milestone payments.
+Added: No new milestone was met in 2023 and during the six months ended June 30, 2024.
+Added: In December 2022, the FDA approved REZLIDHIA capsules for the treatment of adult patients with R/R AML with IDH1 mutation as detected by an FDA-approved test, and we began the commercialization of REZLIDHIA and made it available to patients.
The recommended dosage of REZLIDHIA is 150 mg taken orally twice daily until disease progression or unacceptable toxicity.
19 unchanged sentences
In November 2022, we also announced the publication of data in The Lancet Haematology, which summarizes the Phase 1 results of the Phase 1/2 trial of olutasidenib .
−Removed: The objectives of the first phase of the multi-center, open-label Phase 1/2 trial were to assess the safety, pharmacokinetic and pharmacodynamic profile, and clinical activity of olutasidenib, both as monotherapy and in combination with azacitidine, in patients with treatment-naïve or R/R AML or MDS harboring IDH1 mutations.
+Added: The objectives of the first phase of the multicenter, open-label Phase 1/2 trial were to assess the safety, pharmacokinetic and pharmacodynamic profile, and clinical activity of olutasidenib, both as monotherapy and in combination with azacitidine, in patients with treatment-naïve or R/R AML or MDS harboring IDH1 mutations.
The published data suggest that olutasidenib, with or without azacitidine, was well-tolerated and was associated with improvements in clinical efficacy endpoints in patients with mIDH1 AML.
3 unchanged sentences
In February 2023, we announced peer-reviewed publication data in Blood Advances , which summarize clinical results from the Phase 2 registrational trial of REZLIDHIA in patients with mIDH1 R/R AML.
−Removed: The published data
−Removed: demonstrate that REZLIDHIA induced durable remissions and transfusion independence with a well-characterized safety profile.
+Added: The published data demonstrate that REZLIDHIA induced durable remissions and transfusion independence with a well-characterized safety profile.
The observed efficacy is clinically meaningful and represents a therapeutic advance in this poor prognosis patient population with limited treatment options.
REZLIDHIA demonstrated both a high rate of response and an extended median duration of complete response of 28.1 months, which is more than a year longer than what is reported with the standard of care.
−Removed: In June 2023, we announced the second REZLIDHIA publication in Blood Advances , a review article examining the preclinical and clinical development, and the positioning of olutasidenib in the mIDH1 AML treatment landscape.
+Added: In June 2023, we announced the second REZLIDHIA publication in Blood Advances , a review
+Added: article examining the preclinical and clinical development, and the positioning of REZLIDHIA in the mIDH1 AML treatment landscape.
The review concluded that the approval of REZLIDHIA is a critical addition to the mIDH1 AML treatment landscape.
1 unchanged sentence
In June 2023, we announced presentation of data from an analysis from the Phase 2 study of REZLIDHIA in patients with mIDH1 AML who were previously treated with venetoclax.
−Removed: Data was featured in a poster presentation at the European Hematology Association 2023 Hybrid Congress.
+Added: Data was featured in a poster presentation at the European Hematology Association (EHA) 2023 Hybrid Congress.
The data support REZLIDHIA induced durable remissions in patients with mIDH1 AML in this poor-prognosis patient population who were R/R to venetoclax-based treatment.
In April 2024, we announced a peer-reviewed publication in Leukemia & Lymphoma on data from an analysis of the Phase 2 study evaluating REZLIDHIA in patients with mIDH1 AML who are R/R to prior venetoclax-based regimens.
−Removed: The findings from these analyses suggest that REZLIDHIA alone in combination with azacitidine demonstrated potential efficacy in patients with AML following failure of venetoclax combination therapy.
+Added: The findings from these analyses suggest that REZLIDHIA alone or in combination with azacitidine demonstrated potential efficacy in patients with AML following failure of venetoclax combination therapy.
+Added: In May 2024, we announced the presentation of the five-year results from the registrational Phase 2 trial of REZLIDHIA in R/R mIDH1 AML patients at the 2024 ASCO Annual Meeting and EHA 2024 Hybrid Congress.
+Added: The data published reinforces REZLIDHIA’s efficacy in heavily pretreated patients with mIDH1 AML, including those R/R to prior venetoclax.
+Added: The safety profile was consistent with what was previously reported.
+Added: Further, REZLIDHIA was generally well tolerated in elderly patients with R/R mIDH1 AML and induced durable remissions.
+Added: Despite the challenges of treating elderly patients who had already failed prior AML treatment, the results suggest that elderly patients can benefit from therapy with REZLIDHIA.
+Added: REZLIDHIA was also effective in achieving remission in patients with mIDH1 R/R AML and served as a bridging strategy towards potentially curative allogeneic transplantation in a substantial subset of these previously ineligible patients.
+Added: Additionally, REZLIDHIA was well tolerated in a subset of patients with post-myeloproliferative neoplasms (MPN) mlDH1 AML, a patient population often associated with poor responses to available therapies.
Competitive landscape for REZLIDHIA
6 unchanged sentences
We plan to enter collaborations with third parties to commercialize REZLIDHIA outside of US.
−Removed: GAVRETO (pralsetinib) in metastatic RET fusion-positive NSCLC and advanced thyroid cancers
−Removed: Please refer to related discussions above under “Business Updates”, titled “GAVRETO (pralsetinib) in metastatic RET fusion-positive NSCLC and advanced thyroid cancers” in this Item 2, Management’s Discussion and Analysis of this Quarterly Report on Form 10-Q.
+Added: GAVRETO in metastatic RET fusion-positive NSCLC and advanced thyroid cancers
+Added: RET is a receptor tyrosine kinase that activates multiple downstream pathways involved in cell proliferation and survival.
+Added: RET can be activated by mutation or when a portion of the RET gene that encodes the kinase domain is joined to part of another gene creating a fusion gene that encodes an aberrantly activated RET fusion protein.
+Added: alterations, such as fusions or mutations, drive the growth of multiple tumor types.
+Added: It is estimated that over 230,000 adult patients in the US will be diagnosed with lung cancer in 2024.
+Added: NSCLC is the most common type of lung cancer in the US accounting for 80-85% of all lung cancer diagnoses.
+Added: RET activating fusions are key disease drivers in NSCLC.
+Added: RET fusions are implicated in approximately 1-2% of patients with NSCLC.
+Added: We acquired the rights to research, develop, manufacture and commercialize GAVRETO from Blueprint, pursuant to an Asset Purchase Agreement entered in February 2024.
+Added: GAVRETO is a once daily, small molecule, oral, kinase inhibitor of wild-type RET and oncogenic RET fusions.
+Added: Currently, GAVRETO is one of only two approved RET inhibitors on the market for patients.
+Added: GAVRETO is approved by the FDA for the treatment of adult patients with metastatic RET fusion-positive NSCLC as detected by an FDA-approved test.
+Added: GAVRETO is also approved for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).
+Added: This indication was approved by the FDA under accelerated approval based on overall response rate and duration of response.
+Added: Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial.
+Added: Discussions with the FDA regarding confirmatory requirements are ongoing.
+Added: On June 24, 2024, we announced the completion of the transfer to us of the NDA for GAVRETO, and GAVRETO is commercially available from us in the US by prescription beginning June 27, 2024.
+Added: GAVRETO was co-marketed by Blueprint and Genentech, a member of Roche Group (Roche), to patients in the US since September 2020 pursuant to a collaboration agreement between Blueprint and Roche, which was terminated effective in February 2024.
+Added: The patent portfolio covering pralsetinib contains patents and patent applications directed to compositions of matter for pralsetinib, including solid forms, formulations, and methods of use and manufacture.
+Added: Pralsetinib is covered as a composition of matter in a US issued patent that has an expiration date in November 2036 and subject to potential extensions.
+Added: Patents that have been issued or are expected to be issued covering pralsetinib will have statutory expiration dates between 2036 and 2041.
+Added: The FDA granted GAVRETO new chemical entity exclusivity until September 2025 and orphan drug exclusivity until September 2027 with respect to the approval for treatment of adult patients with metastatic RET fusion-positive NSCLC as detected by an FDA-approved test.
+Added: The FDA also granted GAVRETO two orphan drug exclusivities until December 2027 with respect to FDA approval for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate), and for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid carcinoma who require systemic therapy.
+Added: Competitive landscape for GAVRETO
+Added: GAVRETO faces competition for RET fusion-positive NSCLC and advanced thyroid cancers from Lilly’s selpercatinib.
+Added: In addition, other commercially available therapies used to treat RET fusion-positive NSCLC include cabozantanib and platinum-based chemotherapy regimens with or without pembrolizumab, atezolizumab, nivolumab/ipilumumab, cemiplimab or tremelimumab-durvalumab.
+Added: Pralsetinib may also face competition from other drug candidates in development for RET-altered cancers, as well as multi-kinase inhibitors with RET activity being evaluated in clinical trials.
+Added: Commercial activities, including sales and marketing
+Added: We began our commercialization and started recognizing revenue from product sales of GAVRETO in June 2024.
+Added: We believe GAVRETO is highly synergistic with our current product portfolio, and we expect to continue to leverage our existing commercial infrastructure to ensure current and newly prescribed GAVRETO patients have continued access to this important treatment option.
+Added: We distribute and market GAVRETO for approved indications in RET fusion-positive NSCLC and advanced thyroid cancers.
Clinical Stage Programs
9 unchanged sentences
We advanced the development of our IRAK 1/4 inhibitor program, following further evaluation of single and multiple ascending doses of R289, a new pro-drug formulation of R835 in healthy subjects.
−Removed: In January 2022, we received clearance from the FDA to initiate a Phase 1 open-label, multicenter trial to evaluate the safety, tolerability and preliminary efficacy of R289 in patients with R/R lower-risk MDS.
+Added: In January 2022, we received clearance from the FDA to initiate a Phase 1b open-label, multicenter trial to evaluate the safety, tolerability and preliminary efficacy of R289 in patients with R/R lower-risk MDS.
In December 2022, we announced the dosing of the first patient.
2 unchanged sentences
The safety and efficacy data from this Phase 1b trial is intended to inform the recommended dose of R289 for further clinical evaluation in lower-risk MDS.
−Removed: To date, enrollment in the third cohort of the trial has been completed and we are planning to include two additional cohorts with twice daily dosing regimens.
+Added: To date, enrollment in the fourth dose level (250 mg twice daily) of the trial is underway.
Preliminary data are expected by the end of 2024.
−Removed: Fostamatinib in Hospitalized COVID-19 Patients
−Removed: We had a Phase 3 clinical trial to evaluate the safety and efficacy of fostamatinib in hospitalized COVID-19 patients without respiratory failure that have certain high-risk prognostic factors.
−Removed: The DOD’s Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense awarded us grants to support this trial.
−Removed: The trial completed with 280 patients.
−Removed: We previously announced in November 2022 the top-line results from the trial did not meet statistical significance in the primary efficacy endpoint, which is the number of days the patient on oxygen through Day 29.
−Removed: Upon further analysis, we discovered an error by the biostatistical CRO in the application of a statistical stratification factor.
−Removed: The biostatistical CRO misinterpreted receipt of prior COVID-19 treatment of interest 14 days before randomization (regardless of continuation post randomization), as those medications taken 14 days before the date of randomization and ended prior to the day of randomization.
−Removed: After correcting for this statistical error, the primary endpoint of the study was met;
−Removed: those who received fostamatinib had lower mean days on oxygen than those who received placebo.
−Removed: Further, fostamatinib showed significance or trend towards significance in all secondary endpoints of reducing mortality and morbidity compared to placebo after correcting for the error.
−Removed: Given the end of the federal COVID-19 PHE in May 2023 , and based on feedback from the FDA, DOD and other advisors regarding the program’s regulatory requirements, costs, timeline, and potential for success, we decided not to submit an EUA or sNDA.
−Removed: Fostamatinib had been selected for the Accelerating COVID-19 Therapeutic Inventions and Vaccines Phase 2/3 trial (ACTIV-4 Host Tissue Trial), conducted and sponsored by the National Institute of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) .
−Removed: The ACTIV-4 Host Tissue Trial is a randomized, placebo-controlled trial of therapies, including fostamatinib, targeting the host response to COVID-19 in hospitalized patients.
−Removed: In September 2023, the DSMB recommended that the fostamatinib study arm of the ACTIV-4 Host Tissue Trial platform cease enrollment.
−Removed: Based on the DSMB’s review of a conditional power analysis, the DSMB determined that there was an extremely low
−Removed: likelihood of fostamatinib providing benefits related to the primary outcome (oxygen free days) or other secondary outcomes in patients hospitalized and on oxygen therapy for COVID-19.
−Removed: No safety concerns were identified.
−Removed: The NIH/NHLBI concurs with the DSMB’s recommendation and has asked the trial investigators to cease enrollment, complete follow-up for participants already enrolled, and complete study closeout.
Partnered Clinical Programs
−Removed: Lilly is continuing to advance R552 and has initiated the Phase 2a trial studying R552 in adult patients with moderately to severely active rheumatoid arthritis.
−Removed: The trial plans to enroll 100 patients globally.
+Added: Ocadusertib – Lilly
+Added: Lilly is continuing to advance ocadusertib (previously R552) and has initiated the Phase 2a trial studying ocadusertib in adult patients with moderately to severely active rheumatoid arthritis.
+Added: The Phase 2a enrollment of approximately 100 patients is advancing well, with preliminary analysis of the Phase 2a results anticipated in the first half of 2025.
RIPK1 is implicated in a broad range of key inflammatory cellular processes and plays a key role in tumor necrosis factor signaling, especially in the induction of pro-inflammatory necroptosis.
The program also includes RIPK1 compounds that cross the blood-brain barrier (CNS-penetrants) to address neurodegenerative diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis.
−Removed: BGB324 – BerGenBio
+Added: Bemcentinib – BerGenBio
We have an exclusive, worldwide research, development and commercialization agreement with BerGenBio for our investigational AXL receptor tyrosine kinase inhibitor, R428 (now referred to as bemcentinib (BGB324)).
2 unchanged sentences
Also in March 2023, BerGenBio announced its first patient dosed in a Phase 1b/2a trial evaluating bemcentinib in first-line NSCLC patients harboring STK11 mutations .
−Removed: DS-3032 – Daiichi
+Added: In March 2024, BerGenBio announced initiation of the Phase 2a portion of the study following a positive decision by the Data and Safety Monitoring Board following review of the Phase 1b safety data.
+Added: Milademetan – Daiichi
DS-3032 is an investigational oral selective inhibitor of the MDM2 protein investigated by Daiichi in three Phase 1 clinical trials for solid and hematological malignancies including AML, acute lymphocytic leukemia, chronic myeloid leukemia in blast phase, lymphoma and MDS.
1 unchanged sentence
In September 2020, worldwide rights to DS-3032 (milademetan) were out-licensed from Daiichi to Rain Oncology Inc., formerly Rain Therapeutics Inc.
−Removed: In January 2024, Phatos Al, Inc.
+Added: In January 2024, Pathos Al, Inc.
(Pathos) completed the acquisition of Rain.
1 unchanged sentence
Research, Preclinical and Clinical Development Programs
−Removed: We have retained a selected team of experts in drug discovery and preclinical development to leverage our existing proprietary collection of inhibitors, small-molecule compound libraries and large database of associated phenotypic and biochemical assay results of therapeutic interest.
+Added: We have retained selected experts in drug discovery and preclinical development to leverage our existing proprietary collection of inhibitors, small-molecule compound libraries and large database of associated phenotypic and biochemical assay results of therapeutic interest.
We maintain leading expertise on specific areas of operation such as inhibition of SYK, IRAK 1/4, RIPK1 and mIDH1 kinases to assist clinical development and commercial affairs, as well as to expand and explore additional opportunities for such inhibitors in the clinical space.
Our preclinical operations involve collaborations with clinical research organizations, leading investigators from universities and research organizations around the world, and strategic collaborations with other pharmaceutical companies.
−Removed: We have assembled a team of experts in drug development to design and implement clinical trials and to analyze the data derived from these trials.
+Added: We have experts in drug development to design and implement clinical trials and to analyze the data derived from these trials.
The clinical development group possesses expertise in project management and regulatory affairs.
We work with external clinical research organizations with expertise in managing clinical trials, drug formulation, and the manufacture of clinical trial supplies to support our drug development efforts.
−Removed: We also have strategic development collaborations with MDACC and CONNECT to conduct evaluation of REZLIDHIA (oluatasidenib) in AML, other hematologic cancers and glioma.
+Added: We also have strategic development collaborations with MDACC and CONNECT to conduct evaluation of REZLIDHIA (olutasidenib) in AML, other hematologic cancers and glioma.
Commercialization and Sponsored Research and License Agreements
1 unchanged sentence
Results of Operations
−Removed: Three Months Ended March 31,
+Added: Three Months Ended June 30,
+Added: Six Months Ended June 30,
(in thousands)
1 unchanged sentence
Contract revenues from collaborations
+Added: Government contracts
Total revenues
The following table summarizes the percentages of revenues from each of our customers who individually accounted for 10% or more of the total net product sales and revenues from collaborations:
−Removed: Three Months Ended March 31,
−Removed: McKesson Specialty Care Distribution Corporation
−Removed: Cardinal Healthcare
+Added: Three Months Ended June 30,
+Added: Six Months Ended June 30,
+Added: McKesson Corporation
+Added: Cardinal Health, Inc.
(formerly ASD Healthcare)
Revenue from product sales is related to our sale of our products in the US, net of chargebacks, discounts and fees, government and other rebates and returns.
−Removed: TAVALISSE net product sales in the three months ended March 31, 2024 of $21.1 million decreased by $1.2 million or 5% compared to $22.3 million in the same period in 2023.
−Removed: The decrease was driven partly by a decrease in number of bottles remaining in distributors channels, and partly due to the increase in revenue reserves driven by higher government and private payor rebates.
−Removed: These decreases were partially offset by the increase in price per bottle of TAVALISSE.
−Removed: REZLIDHIA net product sales in the three months ended March 31, 2024 of $4.9 million increased by $3.4 million compared to $1.5 million in the same period in 2023.
+Added: Typically, our first quarter net sales are impacted by the first quarter reimbursement issues such as the resetting of co-pays and the Medicare donut hole.
+Added: TAVALISSE net product sales for the three and six months ended June 30, 2024 were $26.4 million and $47.5 million, respectively, increased by 24% and 9%, respectively, compared to $21.3 million and $43.6 million net product sales for the three and six months ended June 30, 2023, respectively.
+Added: The increase was primarily due to increased quantities sold, as well as increased price per bottle.
+Added: This increase was partially offset by the increase in revenue reserves driven by higher government and private payor rebates.
+Added: REZLIDHIA net product sales in the three and six months ended June 30, 2024 were $5.2 million and $10.0 million, respectively, increased by 102% and 150% compared to $2.6 million and $4.0 million net product sales for the three and six months ended June 30, 2023, respectively.
The increase was primarily due to increased quantities sold primarily driven by increased number of patients under therapy, partially offset by the increase in revenue reserves primarily due to higher government rebates.
−Removed: Contract revenues from collaborations in the three months ended March 31, 2024 consisted of revenue from Kissei of $2.3 million related to the delivery of drug supplies, revenue from Grifols of $1.1 million related to earned royalty, and revenue from Medison of $0.1 million related to the delivery of drug supplies and earned royalty.
−Removed: In the three months ended March 31, 2023, contract revenues from collaborations consisted of revenue from Grifols of $2.3 million related to the delivery of drug supplies and earned royalty, and $0.1 million of revenue from Medison related to the delivery of drug supplies.
−Removed: We expect that our future revenues to include product sales of our existing commercial products, TAVALISSE and REZLIDHIA, product sales from our upcoming commercialization later this year of GAVRETO, and product sales from new commercial products we may have in the future.
+Added: Following the commercialization of GAVRETO on June 27, 2024, we started recognizing revenue from shipments to our distributors.
+Added: During the three and six months ended June 30, 2024, we recognized $1.9 million of GAVRETO net product sales.
+Added: Contract revenues from collaborations in the three and six months ended June 30, 2024 consisted primarily of revenue from Kissei of $2.2 million and $4.5 million, respectively, related to the delivery of drug supplies, and revenue from Grifols of $1.1 million and $2.2 million, respectively, related to earned royalty.
+Added: Contract revenues from collaborations in the three and six months ended June 30, 2023 consisted primarily of revenue from Grifols of $2.0 million and $4.3 million, respectively, related to earned royalty and delivery of drug supplies.
+Added: Government contract revenue in the three and six months ended June 30, 2023 was related to the income we recognized upon achievement of certain milestones from the award granted to us by the DOD.
+Added: No government contract revenue was recognized during the three and six months ended June 30, 2024.
+Added: We expect that our future revenues to include product sales of our existing commercial products and product sales from new commercial products we may have in the future.
Our net product sales may be impacted by the demand from our customers, changes to government and private payor rebate programs, chargeback and discount programs, co-payment assistance programs, and any other rebate and discount programs we may enter in the future.
In addition, our future revenues may include payments from our existing and new collaboration partners and government grants.
−Removed: As of March 31, 2024, we had $1.4 million of deferred revenue relating to our collaboration agreement with Kissei which we will recognize as revenue upon satisfaction of our remaining performance obligations.
+Added: As of June 30, 2024, we had $1.4 million of deferred revenue relating to our collaboration agreement with Kissei which we will recognize as revenue upon satisfaction of our remaining performance obligations.
Cost of Product Sales
−Removed: Three Months Ended March 31,
+Added: Three Months Ended June 30,
+Added: Six Months Ended June 30,
(in thousands)
2 unchanged sentences
Inventories sold for the periods presented include inventory quantities acquired or produced prior to the FDA approval of the product, and do not reflect the full cost of the inventories sold, since such costs incurred prior to FDA approval were previously expensed and charged to research and development expense.
−Removed: In particular, we still utilize active pharmaceutical ingredient with zero cost for our TAVALISSE inventories, which we expect to make use of for the next 2 to 3 years.
+Added: In particular, we still utilize active pharmaceutical ingredients with zero cost for our TAVALISSE inventories, which we expect to make use of for the next 2 to 3 years.
As such, we recognize lower cost of product sales in the periods where we sell inventory quantities acquired or produced prior to the FDA approval of the product.
2 unchanged sentences
We recognize amortization of intangible assets acquired from in-licensing or acquisition of commercialized products as well as royalty expense within cost of sales.
−Removed: The increase in cost of product sales in the three months ended March 31, 2024 compared to the same period in 2023 was primarily due to increased royalty from sale of REZLIDHIA and due to increased delivery of drug supplies pursuant to our supply agreements with our collaborative partners.
+Added: The increase in cost of product sales in the three and six months ended June 30, 2024 compared to the same periods in 2023 was partly due to increased royalty expense and amortization of intangible assets of approximately $0.9 million and $1.5 million, respectively.
+Added: Further, the increase in cost of product sales was also partly due to increased product sales, and increased delivery of drug supplies pursuant to our supply agreements with our collaborative partners.
Research and Development Expense
−Removed: Three Months Ended March 31,
+Added: Three Months Ended June 30,
+Added: Six Months Ended June 30,
(in thousands)
1 unchanged sentence
Stock-based compensation expense included in research and development expense
−Removed: Stock-based compensation expense in the three months ended March 31, 2024 above include an incremental charge of approximately $0.5 million from stock option modifications recorded in the first quarter of 2023 related to the acceleration of vesting and extension of exercise period of vested stock option grants made to a former officer whose employment ended in March 2023.
−Removed: The decrease in research and development expense in three months ended March 31, 2024 compared to the same period in 2023 was partly due decreased in clinical trial related expenses of $1.1 million due to timing of trial activities of our IRAK 1/4 inhibitor program, as well as decreased clinical trial activities of $1.0 million due to timing of trial completion activities of our Phase 3 clinical trials of fostamatinib for the treatment of hospitalized high-risk patients with COVID-19 and wAIHA.
−Removed: Further, personnel-related costs and stock-based compensation expense decreased by $1.0 million and other research and development expense including allocated facilities and laboratory costs decreased by $1.0 million.
+Added: The increase in research and development expense in the three months ended June 30, 2024 compared to the same period in 2023 was primarily due to increased various research and development expenses of $1.6 million due to progress of trial activities of R289, our IRAK 1/4 inhibitor program and other clinical activities.
+Added: The increase was partly offset by decreased clinical trial costs of $0.8 million due to reduced trial activities of our completed Phase 3 clinical trials of fostamatinib in patients with COVID-19 and wAIHA.
+Added: The decrease in research and development expense in six months ended June 30, 2024 compared to the same period in 2023 was partly due to decreased clinical trial activities of $1.8 million due to reduced trial activities of our completed Phase 3 clinical trials of fostamatinib in patients with COVID-19 and wAIHA, as well as $1.2 million decreased clinical trial related expenses due to progress of trial activities of R289, our IRAK 1/4 inhibitor program .
+Added: Other research and development expense including allocated facilities and laboratory costs also decreased by $0.3 million.
Our research and development expenditures include costs related to preclinical and clinical trials, scientific personnel, supplies, equipment, consultants, sponsored research, stock-based compensation, and allocated facility costs.
−Removed: W e expect to continue to incur significant research and development expense as we continue our activities in our clinical studies including our IRAK1/4 inhibitor program;
−Removed: our collaborative partnerships with MDACC and CONNECT to evaluate REZLDHIA (olutasidenib) in AML, other hematologic cancers and glioma;
+Added: W e expect to continue to incur significant research and development expense as we continue our activities in our clinical studies including R289, our IRAK 1/4 inhibitor program;
+Added: our collaborative partnerships with MDACC and CONNECT to evaluate REZLIDIHIA (olutasidenib) in AML, other hematologic cancers and glioma;
and any other clinical programs we may pursue in the future.
2 unchanged sentences
research, development, and other.
−Removed: Our research team is focused on identifying and evaluating product candidates in our focused range of therapeutic indications
−Removed: that can be developed into small molecule therapeutics in our own proprietary programs or with potential collaborative partners.
+Added: Our research team is focused on identifying and evaluating product candidates in our focused range of therapeutic indications that can be developed into small molecule therapeutics in our own proprietary programs or with potential collaborative partners.
“Research” expenses relate primarily to personnel expenses, lab supplies, fees to third-party research consultants and compounds.
14 unchanged sentences
The following table presents our total research and development expense by category (in thousands).
−Removed: Three Months Ended March 31,
+Added: Three Months Ended June 30,
+Added: Six Months Ended June 30,
From January 1, 2007*
−Removed: to March 31, 2024
+Added: to June 30, 2024
* We started tracking research and development expense by category on January 1, 2007.
−Removed: “Other” expenses in the three months ended March 31, 2024 and 2023 consisted of allocated facilities costs of $0.1 million and $0.6 million, respectively, and allocated stock-based compensation expense of $0.7 million and $1.0 million, respectively.
−Removed: The major portion of our total research and development expense in the three months ended March 31, 2024 and 2023 was associated with our IRAK 1/4 inhibitor program.
+Added: “Other” expenses in the three months ended June 30, 2024 and 2023 consisted of allocated facilities costs of $0.2 million and $0.1 million, respectively, and allocated stock-based compensation expense of $0.3 million and $0.4 million, respectively.
+Added: For the six months ended June 30, 2024 and 2023, allocated facilities costs was $0.3 million and $0.8 million, respectively, and allocated stock-based compensation expense was $1.0 million and $1.4 million, respectively.
+Added: The major portion of our total research and development expense in the three and six months ended June 30, 2024 and 2023 was associated with R289, our IRAK 1/4 inhibitor program.
Selling, General and Administrative Expense
−Removed: Three Months Ended March 31,
+Added: Three Months Ended June 30,
+Added: Six Months Ended June 30,
(in thousands)
1 unchanged sentence
Stock-based compensation expense included in selling, general and administrative expense
−Removed: The increase in selling, general and administrative expense in the three months ended March 31, 2024 compared to the same period in 2023 was primarily due to the increase of $2.7 million in stock-based compensation expense primarily from our performance-based stock awards.
−Removed: This was partially offset by the $0.7 million decrease in consulting and other third-party services, decrease of $0.5 million in commercial related expenses primarily driven by the timing of commercialization activities for our new products, and decrease of $0.8 million in other various sales, general and administrative costs primarily due to lower facilities cost.
−Removed: We expect to incur significant selling, general and administrative expenses, as we expect our commercial related expenses to increase as we continue to expand our commercial activities of our existing products, TAVALISSE and REZLIDHIA, and our upcoming commercialization later this year of GAVRETO.
+Added: The increase in selling, general and administrative expense in the three months ended June 30, 2024 compared to the same period in 2023 was primarily due to the increase in personnel-related costs of $1.1 million, increase in stock-based compensation expense of $0.4 million, and increase in other various sales, general and administrative costs of $0.2 million.
+Added: The increase in selling, general and administrative expense in the six months ended June 30, 2024 compared to the same period in 2023 was primarily due to the increase of $3.2 million in stock-based compensation expense primarily from our performance-based stock awards, and increase in personnel-related costs of $1.3 million.
+Added: This was partially offset by the decrease of $2.0 million in other various sales, general and administrative costs primarily due to lower facilities cost.
+Added: We expect to incur significant selling, general and administrative expenses, as we expect our commercial related expenses to increase as we continue to expand our commercial activities for TAVALISSE, REZLIDHIA, and our recently commercialized product, GAVRETO.
We continue to deploy resources to enable our field-based employees to engage with healthcare providers.
1 unchanged sentence
Interest Income and Interest Expense
−Removed: Three Months Ended March 31,
+Added: Three Months Ended June 30,
(in thousands)
2 unchanged sentences
Interest income is related to our interest-bearing cash and investment balances.
−Removed: The increase interest income in the three months ended March 31, 2024 compared to the same period in 2023 was primarily driven by higher interest rates.
+Added: The increase interest income in the three and six months ended June 30, 2024 compared to the same periods in 2023 was primarily driven by higher interest rates.
Interest expense comprised primarily of interest on the outstanding term loan with MidCap.
−Removed: The increase in interest expense in the three months ended March 31, 2024 compared to 2023 was primarily due to higher interest expense on our term loan with Midcap driven by higher loan balance outstanding throughout the period, as the $20.0 million (Tranche 5) was funded in March 2023.
+Added: Increased interest expense in the three and six months ended June 30, 2024 compared to the same periods in 2023 was primarily due to higher interest on our term loan with Midcap.
+Added: Also contributing to higher interest expense for the six months ended June 30, 2024 compared to the same period in 2023 was the higher outstanding principal balance of the term loan throughout the respective periods as the Tranche 5 ($20.0 million) term loan was funded in March 2023.
Critical Accounting Policies and Use of Estimates
9 unchanged sentences
Liquidity and Capital Resources
−Removed: As of March 31, 2024 and December 31, 2023, we had approximately $49.6 million and $56.9 million, respectively, in cash, cash equivalents and short-term investments.
−Removed: We continue to maintain investment portfolios primarily in money market funds, US treasury bills, government-sponsored enterprise securities, and corporate bonds and commercial paper.
+Added: As of June 30, 2024 and December 31, 2023, we had approximately $49.1 million and $56.9 million, respectively, in cash, cash equivalents and short-term investments.
+Added: We continue to maintain investment portfolios primarily in money market funds, US treasury bills, government-sponsored enterprise securities, corporate bonds and commercial paper.
Cash in excess of immediate requirements is invested with regard to liquidity and capital preservation.
3 unchanged sentences
Following summarizes our cash flow activity for the periods presented:
−Removed: Three Months Ended March 31,
+Added: Six Months Ended June 30,
(in thousands)
3 unchanged sentences
Financing activities
−Removed: Net (decrease) increase in cash and cash equivalents
−Removed: Net cash used in operating activities for the three months ended March 31, 2024 and 2023 were primarily due to payments of our operating expenses, partially offset by proceeds received from sales of our existing commercial products, and cash received from our collaboration partners.
−Removed: Net cash used in operating activities for the three months ended March 31, 2023 include $20.0 million regulatory milestone payment from Kissei received in January 2023.
−Removed: Net cash provided by investing activities for the three months ended March 31, 2024 comprised net maturities of short-term investments of $0.5 million, partially offset by a payment for capitalized intangible asset related to the Asset Purchase Agreement with Blueprint of $0.1 million.
−Removed: Net cash provided by investing activities for the three months ended March 31, 2023 comprised maturities of short-term investments of $15.7 million and proceeds from sale of property and equipment of $0.1 million, partially offset by the payment of milestone obligations to Forma recorded as intangible assets of $15.0 million.
−Removed: Net cash used in operating activities for the three months ended March 31, 2024 comprised cost share payments to a collaboration partner of $2.6 million, partially offset by the net proceeds from issuance of common stock upon exercise of stock options.
−Removed: Net cash provided by financing activities for the three months ended March 31, 2023 was primarily due to the net cash proceeds from term loan financing (Tranche 5) of $20.0 million, partially offset by our cost share payments to Lilly of $0.8 million.
+Added: Net increase in cash and cash equivalents
+Added: Net cash used in operating activities for the six months ended June 30, 2024 was primarily due to payments of our operating expenses, partially offset by proceeds received from sales of our existing commercial products, and cash received from our collaboration partners.
+Added: Net cash provided by operating activities for the six months ended June 30, 2023 was primarily due the proceeds from sales of our products, cash received from our collaboration partners including the $20.0 million regulatory milestone payment from Kissei received in January 2023, as well as cash received from government grants, partially offset by the payments of our operating expenses.
+Added: Net cash provided by investing activities for the six months ended June 30, 2024 comprised net maturities of short-term investments of $11.6 million, partially offset by payments for acquisition of intangible assets of $0.4 million.
+Added: Net cash provided by investing activities for the six months ended June 30, 2023 comprised net maturities of short-term investments of $18.6 million and proceeds from sale of property and equipment of $0.1 million, partially offset by the payment of milestone obligations to Forma recorded as intangible assets of $15.0 million.
+Added: Net cash used in financing activities for the six months ended June 30, 2024 comprised cost share payments to a collaboration partner of $3.6 million, partially offset by the net proceeds from issuance of common stock upon exercise of stock options and participation in the Purchase Plan of $0.3 million.
+Added: Net cash provided by financing activities for the six months ended June 30, 2023 was primarily due to the net cash proceeds from term loan financing of $20.0 million (Tranche 5) and proceeds from exercise of stock options and participation in the Purchase Plan of $0.6 million, partially offset by our cost share payments to collaboration partner of $1.8 million.
We believe that our existing capital resources will be sufficient to support our current and projected funding requirements, including the continued commercialization of our products, through at least the next 12 months from the Form 10-Q filing date.
4 unchanged sentences
Under our existing collaboration agreements that we entered in the ordinary course of business, we received or may be entitled to receive upfront cash payments, payments contingent upon specified events achieved by such partners and royalties on any net sales of products sold by such partners under the agreements.
−Removed: As of March 31, 2024, total future contingent payments to us under our existing agreements, excluding terminated agreements, could exceed $1.3 billion if all potential product candidates achieved all of the payment triggering events under all of our current agreements.
+Added: As of June 30, 2024, total future contingent payments to us under our existing agreements could exceed $1.3 billion if all potential product candidates achieved all of the payment triggering events under all of our current agreements.
This estimated future contingent amount does not include any estimated royalties that could be due to us if the partners successfully commercialize any of the licensed products.
1 unchanged sentence
See further discussion in “Note 4 – Sponsored Research, License Agreements and Government Contracts” to our “Notes to Condensed Financial Statements” contained in Part I, Item 1 of this Quarterly Report on Form 10-Q.
−Removed: In August 2020, we entered into an Open Market Sale Agreement with Jefferies LLC (Jefferies), as a sole agent, pursuant to which we may sell from time to time, through Jefferies, shares of our common stock in sales deemed to be “at-the-market offerings” as defined in Rule 415 under the Securities Act, subject to conditions specified in the Open Market Sale Agreement, including maintaining an effective registration statement covering the sale of shares under the Open Market Sale Agreement.
−Removed: We have a shelf registration statement filed with the SEC that was declared effective on May 3, 2022, which registered, among other securities, a base prospectus which covers the offering, issuance, and sale by us of up to $250.0 million in the aggregate of the securities identified from time to time in one or more offerings, which include the $100.0 million of shares of our common stock that may be offered, issued and sold under the Open Market Sale Agreement.
−Removed: As of March 31, 2024, we have not sold any shares of common stock under such Open Market Sale Agreement.
−Removed: We have a Credit Agreement with MidCap that provides for $60.0 million term loan credit facility, which was fully funded as of March 31, 2024.
−Removed: See also “Note 12 – Subsequent Events” to our “Notes to Condensed Financial Statements” contained in Part I, Item 1 of this Quarterly Report on Form 10-Q for additional details of the recent amendment to the Credit Agreement.
+Added: We have an Open Market Sale Agreement with Jefferies LLC (Jefferies), as a sole agent, entered on August 4, 2020, and amended and restated on August 2, 2024.
+Added: Pursuant to such Open Market Sale Agreement, we may sell from time to time, through Jefferies, shares of our common stock in sales deemed to be “at-the-market offerings” as defined in Rule 415 under the Securities Act, subject to conditions specified in the Open Market Sale Agreement, including maintaining an effective registration statement covering the sale of shares under the Open Market Sale Agreement.
+Added: We have a shelf registration statement (the Prior Registration Statement) filed with the SEC that includes a base prospectus registering the offering, issuance, and sale by us of up to $250.0 million in the aggregate of the securities identified from time to time in one or more offerings, which include the $100.0 million of shares of our common stock that may be offered, issued and sold under the Open Market Sale Agreement.
+Added: As of June 30, 2024, we have not sold any shares of common stock under such Open Market Sale Agreement.
+Added: The Prior Registration Statement was set to expire on August 3, 2024.
+Added: On August 2, 2024, we filed a new shelf registration statement (the New Registration Statement) with the SEC to replace the Prior Registration Statement.
+Added: The New Registration Statement includes a base prospectus to register the offering, issuance and sale by us of up to $250.0 million in the aggregate of securities identified from time to time in one or more offerings, including up to $100.0 million of shares of our common stock that may be offered, issued and sold under the Open Market Sale Agreement.
+Added: Under Rule 415(a)(5) under the Securities Act, we may offer and sell any unsold securities under the Prior Registration Statement until the SEC declares the New Registration Statement effective.
+Added: Once the New Registration Statement is declared effective, all offerings under the Prior Registration Statement will be terminated.
+Added: We have a Credit Agreement with MidCap that provides for $60.0 million term loan credit facility, which was fully funded as of June 30, 2024.
Our operations will require significant additional funding in the foreseeable future.
27 unchanged sentences
We do not have any purchase commitments under any collaboration arrangements.
−Removed: We have agreements with certain clinical research organizations to conduct our clinical trials including our recent strategic development collaborations with MDACC and CONNECT, as well as with third parties relative to our commercialization of our products.
+Added: We have agreements with certain clinical research organizations to conduct our clinical trials including our strategic development collaborations with MDACC and CONNECT, as well as with third parties relative to our commercialization of our products.
The timing of payments for any amounts owed under the respective agreements will depend on various factors including, but not limited to, patient enrollment and other progress of the clinical trials, and various activities related to commercialization.
3 unchanged sentences
In addition, these agreements may, from time to time, be subjected to amendments as a result of any change orders executed by the parties.
−Removed: As discussed in detail in “Note 4 – Sponsored Research, License Agreements and Government Contracts” of our “Notes to Condensed Financial Statements” contained in Part I, Item 1 of this Quarterly Report on Form 10-Q, pursuant to the amended Lilly Agreement, and us providing the first opt-out notice to Lilly on September 29, 2023, we are responsible for funding the development costs for R552 in the US, Europe, and Japan, up to $22.6 million through April 1, 2024.
−Removed: Through March 31, 2024, Lilly billed us $20.3 million of the funding development costs incurred as of the fourth quarter of 2023, and the amount was fully paid as of March 31, 2024.
−Removed: The amended Lilly Agreement, however, provides us the right to opt-in to co-funding the R552 development, upon us providing notice to Lilly within 30 days of certain events, as specified in the Lilly Agreement.
+Added: As discussed in detail in “Note 4 – Sponsored Research, License Agreements and Government Contracts” of our “Notes to Condensed Financial Statements” contained in Part I, Item 1 of this Quarterly Report on Form 10-Q, pursuant to the amended Lilly Agreement, and us providing the first opt-out notice to Lilly on September 29, 2023, we were responsible for funding the development costs for ocadusertib (previously R552) in the US, Europe, and Japan, through April 1, 2024, capped at a specified amount.
+Added: Lilly billed us $21.4 million of the funding development costs incurred through April 1, 2024 and the amount was fully paid as of June 30, 2024.
+Added: Although currently we are no longer obligated to pay Lilly for our share in the ocadusertib development cost incurred subsequent to April 1, 2024, under the Lilly Agreement, we have the right to opt-in to co-funding the ocadusertib development, upon us providing notice to Lilly within 30 days of certain events, as specified in the Lilly Agreement.
If we decide to exercise our opt-in right, we will be required to continue to share in global development costs, and if we later exercise our second opt-out right (no later than April 1, 2025), our share in global development costs will be up to a specified cap through December 31, 2025, as provided for in the Lilly Agreement.
−Removed: As discussed in detail in “Note 5 – In-licensing and Acquisition” of our “Notes to Condensed Financial Statements” contained in Part I, Item 1 of this Quarterly Report on Form 10-Q, pursuant to an Asset Purchase Agreement with Blueprint entered in February 2024, we agreed to pay Blueprint a purchase price of $15.0 million, $10.0 million of which is payable upon our first commercial sale of GAVRETO (pralsetinib) and an additional $5.0 million of which is payable on the first anniversary of the closing date of the agreement, subject to certain conditions.
+Added: As discussed in detail in “Note 5 – In-licensing and Acquisition” of our “Notes to Condensed Financial Statements” contained in Part I, Item 1 of this Quarterly Report on Form 10-Q, pursuant to an Asset Purchase Agreement with Blueprint entered in February 2024, we agreed to pay Blueprint a purchase price of $15.0 million, of which, $10.0 million was paid in July 2024 following our first commercial sale of GAVRETO at end of June 2024, and an additional $5.0 million is payable on the first anniversary of the closing date of the agreement, subject to certain conditions.
Blueprint is also eligible to receive up to $97.5 million in future commercial milestone payments and up to $5.0 million in future regulatory milestone payments, in addition to tiered royalties ranging from 10% to 30%.
−Removed: Simultaneously and in conjunction with entering into the Asset Purchase Agreement, we also entered into certain supporting agreements, including a customary transition agreement, pursuant to which, during the transition period, Blueprint will transition regulatory and distribution responsibility for GAVRETO (pralsetinib) to us.
−Removed: We also agreed to purchase certain drug product inventories from Blueprint amounting to approximately $7.0 million under a Material Transfer Agreement.
−Removed: As of March 31, 2024, we received inventories amounting to approximately $3.1 million, and the remaining inventories are expected to be delivered to us in the second quarter of 2024.
Additionally, as discussed in detail in “Note 5 – In-licensing and Acquisition” of our “Notes to Condensed Financial Statements” contained in Part I, Item 1 of this Quarterly Report on Form 10-Q, pursuant to our license and transition services agreement, Forma is entitled to potential development and regulatory milestone payments of up to $67.5 million, commercial milestone payments of up to $165.5 million, and tiered royalty payments.
In 2022, certain milestones were met which entitled Forma to receive $17.5 million milestone payments, of which, $2.5 million was paid in the fourth quarter of 2022 and $15.0 million was paid in the first quarter of 2023.
−Removed: No new milestone was met in 2023 and during the three months ended March 31, 2024.
−Removed: As of March 31, 2024, we have a contractual commitment related to our leased facilities of $0.9 million, with approximately $0.7 million payable within 12 months.
+Added: No new milestone was met in 2023 and during the six months ended June 30, 2024.
+Added: As of June 30, 2024, we have a contractual commitment related to our leased facilities of $0.7 million and the amount is payable within 12 months.
See “Note 11 – Leases” to our “Notes to Condensed Financial Statements” contained in Part I, Item 1 of this Quarterly Report on Form 10-Q for further discussions of our leases.
−Removed: As discussed above, we have a contractual commitment with respect to our credit facility with MidCap, and as of March 31, 2024, the outstanding principal amount of the loan was $60.0 million.
−Removed: As discussed in detail in “Note 12 – Subsequent Events” to our “Notes to Condensed Financial Statements” contained in Part I, Item 1 of this Quarterly Report on Form 10-Q, in April 2024, we entered into Fourth Amendment to the Credit Agreement with MidCap, which among other things, (i) extended the maturity date for the term loans to September 1, 2027, (ii) extended the interest only period for the term loans to October 1, 2025, (iii) revised the interest rate payable on the term loans to SOFR plus an adjustment of 0.11448%, subject to 4.00% applicable floor, plus applicable margin of 6.50%, (iv) reset the prepayment fee applicable to the term loans, (v) increased the exit fee payable on the term loans to 4.25% and (vi) updated certain financial covenants in connection with the new maturity date.
−Removed: Following the Amended Credit Agreement which extended the interest only period for the term loans to October 1, 2025, no principal payments is due within 12 months.
−Removed: Further, as of March 31, 2024, future interest including final fee calculated following the Fourth Amendment to the Credit Agreement amounted to $19.3 million, of which, approximately $6.6 million is payable within 12 months.
+Added: As discussed above, we have a contractual commitment with respect to our credit facility with MidCap, and as of June 30, 2024, the outstanding principal amount of the loan was $60.0 million.
+Added: As discussed in detail in “Note 10 – Debt” to our “Notes to Condensed Financial Statements” contained in Part I, Item 1 of this Quarterly Report on Form 10-Q, the term loans mature on September 1, 2027, and the interest-only period is through October 1, 2025.
+Added: The term loans bear interest equal to the sum of one-month SOFR plus an adjustment of 0.11448%, subject to a 4.00% applicable floor, plus applicable margin of 6.50%.
+Added: A final payment fee of 4.25% of principal is due at maturity date.
+Added: As of June 30, 2024, no principal payments are due within 12 months.
+Added: As of June 30, 2024, future interest calculated using the base interest rate as per the amended Credit Agreement, and the final fee payments associated with the credit facility amounted to $17.6 million, of which, approximately $6.6 million is payable within 12 months.
We are also subject to claims related to the patent protection of certain of our technologies, as well as purported securities class action lawsuit, other litigations, and other contractual agreements.
We are required to assess the likelihood of any adverse judgments or outcomes to these matters as well as potential ranges of probable losses.
−Removed: A determination of the amount of reserves required, if any, for these contingencies is made after careful analysis of each
−Removed: individual matter.
+Added: A determination of the amount of reserves required, if any, for these contingencies is made after careful analysis of each individual matter.
We do not have other material contractual commitments with respect to matters discussed above.
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.