On February 11, 2025 Royalty Pharma plc (Nasdaq: RPRX) reported financial results for the fourth quarter and full year 2024 and introduced full year 2025 guidance for Portfolio Receipts (Press release, Royalty Pharma , FEB 11, 2025, View Source [SID1234650175]).

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

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

                  Schedule Your 30 min Free Demo!

"We had an incredibly successful 2024, delivering double-digit growth in Royalty Receipts, which was significantly above our initial guidance, and deploying $2.8 billion of capital on value-enhancing royalties" said Pablo Legorreta, Royalty Pharma’s founder and Chief Executive Officer. "We are very excited for the opportunities ahead as the fundamentals of our business have never been stronger. Additionally, we have already taken two major steps at the start of 2025 to enhance shareholder value, announcing the acquisition of our external manager, which is expected to result in multiple financial and strategic benefits, and a new $3 billion share repurchase program, which highlights the confidence we have in our business and the attractive value we see in our shares. With a robust transaction pipeline and significant financial flexibility, I am confident that Royalty Pharma is well positioned to deliver attractive, compounding growth over the long term."

Strong Royalty Receipts growth; Portfolio Receipts growth impacted by a high base of comparison

•
Royalty Receipts grew 12% to $729 million in the fourth quarter and 13% to $2,771 million for full year 2024, driven by strong performance from Evrysdi, the CF franchise, Trelegy, Tremfya and new royalty acquisitions.

•
Portfolio Receipts increased 1% to $742 million in the fourth quarter of 2024; Portfolio Receipts decreased 8% from $3,049 million to $2,801 million for full year 2024, largely reflecting $525 million in Biohaven-related milestone payments received in 2023.

Capital Deployment of $2.8 billion in 2024 with royalties on eight new therapies added to the portfolio

•
Record year for synthetic royalty transactions for Royalty Pharma with $925 million announced in 2024.

•
Significantly expanded development-stage portfolio by acquiring royalties on four potential new therapies.

Exciting new product launches expected across the royalty portfolio in 2025

•
Royalty Pharma to benefit in 2025 from new product launches, including Servier’s Voranigo, Bristol Myers Squibb’s Cobenfy, Ascendis’ Yorvipath, Syndax and Incyte’s Niktimvo and Geron’s Rytelo.

Financial guidance for full year 2025 (excludes contribution from future transactions)

•
Royalty Pharma expects 2025 Portfolio Receipts to be between $2,900 million and $3,050 million, representing expected growth of 4% to 9%.

Financial & Liquidity Summary

Three Months Ended
December 31, Twelve Months Ended
December 31,
(unaudited)
($ and shares in millions) 2024 2023 Change 2024 2023 Change
Portfolio Receipts

742 736 1% 2,801 3,049 (8)%
Net cash provided by operating activities

743 773 (4)% 2,769 2,988 (7)%
Adjusted EBITDA (non-GAAP)*

669 682 (2)% 2,565 2,806 (9)%
Portfolio Cash Flow (non-GAAP)*

678 687 (1)% 2,452 2,708 (9)%
Weighted average Class A ordinary shares outstanding – diluted

589 598 (1)% 594 603 (1)%

*
See "Liquidity and Capital Resources" section. Adjusted EBITDA and Portfolio Cash Flow are non-GAAP liquidity measures calculated in accordance with the credit agreement.

Portfolio Receipts Highlights

Three Months Ended December 31,
(unaudited)
($ in millions) 2024 2023 Change
Products:

Marketers: Therapeutic Area:
Cystic fibrosis franchise

Vertex Rare disease 237 207 14%
Trelegy

GSK Respiratory 74 60 23%
Tysabri

Biogen Neuroscience 61 68 (11)%
Evrysdi

Roche Rare disease 56 20 182%
Xtandi

Pfizer, Astellas Cancer 46 38 20%
Imbruvica

AbbVie, J&J Cancer 46 50 (10)%
Promacta

Novartis Hematology 44 44 (1)%
Tremfya

Johnson & Johnson Immunology 39 35 11%
Cabometyx/Cometriq

Exelixis, Ipsen, Takeda Cancer 20 18 11%
Spinraza

Biogen Rare disease 15 17 (13)%
Orladeyo

BioCryst Rare disease 11 8 36%
Trodelvy

Gilead Cancer 11 10 10%
Erleada

Johnson & Johnson Cancer 11 9 25%
Nurtec ODT/Zavzpret

Pfizer Neuroscience 7 5 49%
Other products(5)

54 63 (14)%

Royalty Receipts

729 651 12%
Milestones and other contractual receipts

13 84 (85)%

Portfolio Receipts

742 736 1%
Results for full year 2024 and 2023 are shown in Table 5. Amounts shown in the table may not add due to rounding.

Royalty Receipts was $729 million in the fourth quarter of 2024, an increase of 12% as compared to $651 million in the fourth quarter of 2023. The increase was primarily driven by strong growth from Evrysdi, the cystic fibrosis franchise, Trelegy, Xtandi and Tremfya. Royalty receipts from Evrysdi included the benefit of the additional royalties acquired in October 2023 and June 2024.

Portfolio Receipts was $742 million in the fourth quarter of 2024, an increase of 1% as compared to $736 million in the fourth quarter of 2023. The increase was primarily driven by the same Royalty Receipts increases noted above, offset by a decrease in milestones and other contractual receipts, which reflected a $50 million payment related to the oral formulation of zavegepant in the prior period.

Liquidity and Capital Resources

Royalty Pharma’s liquidity and capital resources are summarized below:

As of December 31, 2024, Royalty Pharma had cash and cash equivalents of $929 million and total debt with principal value of $7.8 billion.

During the fourth quarter of 2024, Royalty Pharma repurchased approximately two million Class A ordinary shares for $50 million. For full year 2024, Royalty Pharma repurchased approximately eight million Class A ordinary shares for $230 million. The weighted-average number of diluted Class A ordinary shares outstanding for the fourth quarter of 2024 was 589 million as compared to 598 million for the fourth quarter of 2023. The weighted-average number of diluted Class A ordinary shares outstanding for full year 2024 was 594 million as compared to 603 million for full year 2023.

In January 2025, Royalty Pharma’s Board of Directors authorized a new share repurchase program under which Royalty Pharma may repurchase up to $3.0 billion of its Class A ordinary shares. Royalty Pharma intends to repurchase $2.0 billion of its shares in 2025, subject to market conditions. The total value of shares repurchased will depend on the discount to the intrinsic value at which its Class A ordinary shares are trading. This new share repurchase program replaces the unused $465 million of the company’s original $1.0 billion share repurchase program that was announced in March 2023.

Liquidity Summary

Three Months Ended
December 31, Twelve Months Ended
December 31,
(unaudited)
($ in millions) 2024 2023 2024 2023
Portfolio Receipts

742 736 2,801 3,049
Payments for operating and professional costs

(72) (54) (236) (243)
Adjusted EBITDA (non-GAAP)

669 682 2,565 2,806
Interest received/(paid), net

8 5 (113) (98)
Portfolio Cash Flow (non-GAAP)

678 687 2,452 2,708
Amounts may not add due to rounding.

•
Adjusted EBITDA (non-GAAP) was $669 million in the fourth quarter of 2024. Adjusted EBITDA is calculated as Portfolio Receipts minus payments for operating and professional costs.

•
Portfolio Cash Flow (non-GAAP) was $678 million in the fourth quarter of 2024. Portfolio Cash Flow is calculated as Adjusted EBITDA minus interest paid or received, net. This measure reflects the cash generated by Royalty Pharma’s business that can be redeployed into value-enhancing royalty acquisitions, used to repay debt, returned to shareholders through dividends or share purchases, or utilized for other discretionary investments.

Refer to Table 4 for Royalty Pharma’s reconciliation of each non-GAAP measure to the most directly comparable GAAP financial measure, net cash provided by operating activities.

Capital Deployment was $522 million in the fourth quarter of 2024, consisting primarily of the acquisitions of royalties on Niktimvo and Rytelo. Capital Deployment reflects cash payments during the period for new and previously announced transactions. Capital Deployment was $2.8 billion for full year 2024.

The table below details Capital Deployment by category:

Capital Deployment

Three Months Ended
December 31, Twelve Months Ended
December 31,
(unaudited)
($ in millions) 2024 2023 2024 2023
Acquisitions of financial royalty assets

(496) (1,002) (2,506) (2,116)
Development-stage funding payments – upfront and milestone

—  —  —  (50)
Development-stage funding payments – ongoing

(1) (1) (2) (2)
Purchases of available for sale debt securities

—  —  (150) — 
Milestone payments

(25) —  (75) (12)
Investments in equity method investees

—  (2) (11) (13)
Acquisitions of other financial assets

—  —  (18) — 
Contributions from legacy non-controlling interests – R&D

0 0 1 1

Capital Deployment

(522) (1,005) (2,761) (2,192)

Amounts may not add due to rounding.

In January 2025, Royalty Pharma announced the sale of the MorphoSys Development Funding Bonds for $511 million in upfront cash (press release). This payment, combined with payments previously received, results in total cash proceeds of $530 million on the $300 million investment that was made in September 2022. The proceeds strengthen Royalty Pharma’s balance sheet and provide added flexibility to pursue its disciplined capital allocation strategy.

Royalty Transactions

For full year 2024, Royalty Pharma announced new transactions of up to approximately $2.8 billion. The announced transactions amount reflects the entire amount of capital committed for new transactions during the year, including potential future milestones.

Recent transactions include:

•
In November 2024, Royalty Pharma acquired a synthetic royalty on Rytelo from Geron Corporation for an upfront payment of $125 million (press release). Rytelo is approved for the treatment of certain adult patients with low- to intermediate-1 risk myelodysplastic syndromes with transfusion-dependent anemia. Following the acquisition, Royalty Pharma is entitled to receive tiered royalties on U.S. net sales on Rytelo.

•
In November 2024, Royalty Pharma acquired a synthetic royalty on Niktimvo from Syndax Pharmaceuticals, Inc. for an upfront payment of $350 million (press release). Niktimvo is approved for the treatment of chronic graft-versus-host disease and will be co-commercialized by Incyte. Following the acquisition, Royalty Pharma is entitled to receive royalties on U.S. net sales on Niktimvo.

The information in this section should be read together with Royalty Pharma’s reports and documents filed with the SEC at www.sec.gov and the reader is also encouraged to review all other press releases and information available in the Investors section of Royalty Pharma’s website at www.royaltypharma.com.

Internalization Transaction

In January 2025, Royalty Pharma agreed to acquire its external manager, RP Management, LLC (the "Manager") (press release). This transaction to simplify Royalty Pharma’s corporate structure is expected to result in multiple benefits for shareholders. On a financial basis, the acquisition is expected to reduce costs and enhance economic returns on investments. Specifically, the acquisition will generate cash savings of greater than $100 million in 2026, rising to greater than $175 million in 2030 and driving cumulative savings of greater than $1.6 billion over ten years. The acquisition also increases shareholder alignment, enhances corporate governance, ensures management continuity and simplifies Royalty Pharma’s corporate structure.

The total transaction value of approximately $1.1 billion(7) consists of approximately 24.5 million shares of Royalty Pharma equity that will vest over five to nine years, approximately $100 million in cash(8), and the assumption of $380 million of the Manager’s existing debt.

The closing of the internalization transaction is subject to shareholders’ approval of the issuance of the share consideration and other customary closing conditions, including required regulatory approvals. The transaction is estimated to close during the second quarter of 2025.

Key Developments Relating to the Portfolio

The key developments related to Royalty Pharma’s royalty interests are discussed below based on disclosures from the marketers of the products.

TEV-‘749 In January 2025, Teva announced that TEV-‘749 (olanzapine LAI) achieved Phase 3 targeted injections without PDSS (post-injection delirium/sedation syndrome), and the full safety presentation is expected in the second quarter of 2025.
Cystic fibrosis franchise
In December 2024, Vertex announced the U.S. Food and Drug Administration (FDA) approval of the new triple-combination modulator Alyftrek (vanzacaftor triple) for the treatment of cystic fibrosis in people ages 6 and older with at least one responsive mutation.

In November 2024, Vertex announced that it had completed regulatory submissions for the vanzacaftor triple in the European Union, the United Kingdom, Canada, Australia, New Zealand and Switzerland, and reviews are underway.

Skytrofa In December 2024, Ascendis announced the U.S. FDA accepted for review its supplemental Biologics License Application (sBLA) in adult growth hormone deficiency for Skytrofa. The FDA set a Prescription Drug User Fee Act (PDUFA) goal date of July 27, 2025.
aficamten In December 2024, Cytokinetics announced that the FDA accepted its New Drug Application (NDA) for aficamten for the treatment of Obstructive Hypertrophic Cardiomyopathy. The FDA has assigned the NDA a Prescription Drug User Fee Act date of September 26, 2025. Additionally, the European Medicines Agency validated the Marketing Authorization Application for aficamten, and it will now be reviewed by the Committee for Medicinal Products for Human Use (CHMP).
Trodelvy In November 2024, Gilead announced plans to voluntarily withdraw the U.S. accelerated approval of Trodelvy for use in pre-treated adult patients with locally advanced or metastatic urothelial cancer, following the results of the Phase 3 TROPiCS-04 trial.

Airsupra In October 2024, AstraZeneca announced that positive high-level results from the BATURA Phase 3b trial showed Airsupra met the primary endpoint, demonstrating a statistically significant and clinically meaningful reduction in the risk of a severe exacerbation when used as an as-needed rescue medication in response to symptoms compared to as-needed albuterol. These positive results triggered a milestone payment from AstraZeneca, of which Royalty Pharma received its pro rata portion of $27 million in January 2025.
MK-8189 In October 2024, Merck updated its public disclosures to remove MK-8189 from its pipeline chart and Royalty Pharma does not anticipate making a further investment in this program.
pelabresib In October 2024, Novartis announced that based on its review of 48-week data from the Phase 3 MANIFEST-2 study, longer follow-up time is needed to determine the regulatory path for pelabresib in myelofibrosis. Novartis will continue to follow patients in MANIFEST-2 and evaluate the potential for additional studies to support registration.
trontinemab In October 2024, Roche presented its latest Phase 1b/2a interim results for trontinemab at the Clinical Trials on Alzheimer’s Disease (CTAD) conference, which demonstrated rapid and robust amyloid plaque depletion after 12 to 28 weeks of treatment and an overall favorable safety profile with very limited amyloid related imaging abnormalities (ARIA-E) observed.
2025 Financial Outlook

Royalty Pharma has provided guidance for full-year 2025, excluding new transactions and borrowings announced after the date of this release, as follows:

Provided February 11, 2025

Portfolio Receipts
$2,900 million to $3,050 million

(Growth of ~+4% to 9% year/year)

Payments for operating and professional costs Approximately 10% of Portfolio Receipts(1)
Interest paid $260 million
The above Portfolio Receipts guidance represents expected growth of 4% to 9% in 2025. Royalty Pharma’s full-year 2025 guidance reflects a negligible estimated foreign exchange impact to Portfolio Receipts, assuming current foreign exchange rates prevail for the rest of 2025.

2025 guidance for payments for operating and professional costs and interest paid does not reflect the impact of the internalization transaction announced on January 10, 2025 and will be updated following the closing of the internalization transaction, which is expected to be in the second quarter of 2025.

Total interest paid is based on the semi-annual interest payment schedule of Royalty Pharma’s existing notes and is anticipated to be approximately $260 million in 2025. Interest paid is anticipated to be approximately $138 million in the first quarter of 2025, which includes the first interest payment on the $1.5 billion notes issued in June 2024. Interest paid in the third quarter of 2025 is anticipated to be $119 million. De minimis amounts are anticipated in the second and fourth quarter of 2025. These projections assume no additional debt financing in 2025, including no drawdown on the revolving credit facility. In 2024, Royalty Pharma collected interest of $46 million on its cash and cash equivalents.

Royalty Pharma today provides this guidance based on its most up-to-date view of its prospects. This guidance assumes no major unforeseen adverse events or changes in foreign exchange rates and excludes the contributions from transactions announced subsequent to the date of this press release.

Financial Results Call

Royalty Pharma will host a conference call and simultaneous webcast to discuss its fourth quarter and full year 2024 results today at 8:30 a.m., Eastern Time. Please visit the "Investors" page of the company’s website at View Source to obtain conference call information and to view the live webcast. A replay of the conference call and webcast will be archived on the company’s website for at least 30 days.

On February 11, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the U.S. Food and Drug Administration (FDA) has accepted for review the resubmission of the Biologics License Application (BLA) for linvoseltamab for the treatment of adult patients with relapsed/refractory (R/R) multiple myeloma (MM) who have received at least four prior lines of therapy or those who received three prior lines of therapy and are refractory to the last line of therapy (Press release, Regeneron, FEB 11, 2025, View Source [SID1234650174]). The target action date for the FDA decision is July 10, 2025.

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

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

                  Schedule Your 30 min Free Demo!

Acceptance of the BLA resubmission follows the resolution of third-party fill/finish manufacturing issues, which was the sole approvability issue identified by the FDA in the previous submission. The BLA is supported by data from the pivotal LINKER-MM1 trial investigating linvoseltamab in R/R MM, and linvoseltamab is also under review by the European Medicines Agency (EMA) for the same patient population.

Linvoseltamab is investigational and has not been approved by any regulatory authority.

About Multiple Myeloma
As the second most common blood cancer, there are over 187,000 new cases of MM diagnosed globally every year, with more than 36,000 diagnosed and 12,000 deaths anticipated in the U.S. in 2025. In the U.S., there are approximately 8,000 people who have MM that has progressed after three lines of therapy, and 4,000 whose disease has progressed after four or more therapies. The disease is characterized by the proliferation of cancerous plasma cells (MM cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Despite treatment advances, MM is not curable and while current treatments are able to slow progression of the cancer, most patients will ultimately experience cancer progression and require additional therapies.

About the Linvoseltamab Clinical Development Program
Linvoseltamab is an investigational BCMAxCD3 bispecific antibody designed to bridge B-cell maturation antigen (BCMA) on MM cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing.

The ongoing, open-label, multicenter Phase 1/2 dose-escalation and dose-expansion LINKER-MM1 trial is investigating linvoseltamab in 282 enrolled patients with relapsed/refractory MM. The Phase 1 dose-escalation portion of the trial – which is now complete – primarily assessed safety, tolerability and dose-limiting toxicities across nine dose levels of linvoseltamab and explored different administration regimens. The ongoing Phase 2 dose expansion portion is assessing the safety and anti-tumor activity of linvoseltamab, with the primary endpoint of objective response rate. Key secondary endpoints include duration of response, progression-free survival, rate of minimum residual disease negative status and overall survival.

Eligibility in the Phase 2 portion requires patients to have received at least three prior lines of therapy or have triple-class refractory MM. Linvoseltamab is administered with an initial step-up dosing regimen followed by the full 200 mg dose administered weekly. At week 16, all patients transition to every two-week dosing. A response-adapted regimen further enables patients to shift to every four-week dosing if they achieve a very good partial response or better and have completed at least 24 weeks of therapy. The regimen requires a total of two 24-hour hospitalizations for safety monitoring.

Linvoseltamab is being investigated in a broad clinical development program exploring its use as a monotherapy as well as in combination regimens across different lines of therapy in MM, including earlier lines of treatment, as well as plasma cell precursor disorders. They include evaluating linvoseltamab in a Phase 1b trial (LINKER-MM2) in combination with other cancer treatments in R/R MM as well as a Phase 3 confirmatory trial (LINKER-MM3) as a monotherapy in R/R MM. For more information on Regeneron’s clinical trials in blood cancer, visit the clinical trials website, or contact via [email protected] or 844-734-6643.

On February 11, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that it will webcast management participation as follows (Press release, Regeneron, FEB 11, 2025, View Source [SID1234650173]):

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

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

                  Schedule Your 30 min Free Demo!

TD Cowen 45th Annual Health Care Conference at 11:50 a.m. ET on Tuesday, March 4, 2025
Leerink Partners 2025 Global Healthcare Conference at 8:00 a.m. ET on Tuesday, March 11, 2025

The sessions may be accessed from the "Investors & Media" page of Regeneron’s website at View Source Replays and transcripts of the webcasts will be archived on the Company’s website for at least 30 days.

On February 11, 2025 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported it has received first country regulatory approval in Europe to begin recruiting for its Phase 3 pivotal trial protocol evaluating Annamycin in combination with Cytarabine (also known as "Ara-C" and for which the combination of Annamycin and Ara-C is referred to as "AnnAraC") for the treatment of AML patients who are refractory to or relapsed after induction therapy (R/R AML) (MB-108) (Press release, Moleculin, FEB 11, 2025, https://moleculin.com/moleculin-receives-first-country-approval-in-europe-to-begin-recruiting-for-the-miracle-phase-3-r-r-acute-myeloid-leukemia-aml-pivotal-trial/ [SID1234650172]). In Ukraine the final necessary regulatory approvals from the Ministry of Health were received last week. This Phase 3 "MIRACLE" trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) will be a global trial, including sites in the US, Europe and the Middle East.

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

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

                  Schedule Your 30 min Free Demo!

"We continue to make solid progress across our site initiation and enrollment efforts. Achieving this important milestone of receiving our first country’s approval puts us another step closer to getting this study well underway and further bolsters our confidence that we’re on track for unblinded preliminary data from the first 45 subjects in the second half of this year. Our team remains committed to operational execution and face-to-face meetings with investigators, over 30 investigators in 11 countries of which I personally have met," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin. "Building on this momentum, we are focused on getting more of the initial 25 sites we have selected to date on board and enrolling for the study."

The MIRACLE study, subject to appropriate future filings with and potential additional feedback from the FDA and their foreign equivalents, utilizes an adaptive design whereby the first 75 to 90 subjects will be randomized (1:1:1) in Part A of the trial to receive high dose cytarabine (HiDAC) combined with either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin, which Annamycin doses were specifically recommended by the FDA in the Company’s end of Phase 1B/2 meeting. The amended protocol allows for the unblinding of preliminary primary efficacy data (Complete Remission or CR) and safety/tolerability of the three arms at 45 subjects, in addition to the conclusion of Part A (at 75 to 90 subjects). This early unblinding will yield 30 subjects with Annamycin (190mg/m2 and 230/m2) and HiDAC and 15 subjects with just HiDAC. The Company expects to reach the first unblinding (45 subjects) in the second half of 2025, in addition to the second unblinding, which is expected in the first half of 2026. This accelerated estimated timeline is due to the positive response the Company received in meetings during December with potential investigators regarding recruitment for the trial.

For Part B of the trial, approximately 244 additional subjects will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimum dose of Annamycin (randomized 1:1). The selection of the optimum dose will be based on the overall balance of safety, pharmacokinetics and efficacy, consistent with the FDA’s new Project Optimus initiative. This increase from 240 to 244 subjects represents the statistical "cost" of the additional interim unblinding.

For more information about the MIRACLE trial, visit clinicaltrials.gov and reference identifier NCT06788756.

Annamycin currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of relapsed or refractory acute myeloid leukemia, in addition to Orphan Drug Designation for the treatment of soft tissue sarcoma. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia from the European Medicines Agency (EMA).

On February 11, 2025 IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company developing innovative gamma-delta T cell therapies, reported encouraging new clinical data from the ongoing Phase 1 investigator-sponsored trial of INB-100, an allogeneic gamma-delta T cell therapy designed to help patients with complex leukemias, including AML (Press release, In8bio, FEB 11, 2025, View Source [SID1234650171]). INB-100, given following hematopoietic stem cell transplantation (HSCT), is demonstrating the potential to achieve durable long-term remissions and improved survival. The data will be presented at the 2025 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, hosted in Honolulu, HI.

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

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

                  Schedule Your 30 min Free Demo!

Highlights

100% of AML patients remain relapse-free
All treated AML patients in both the original and expansion cohorts through January 17, 2025 remain in complete remission. The original cohort of AML patients has reached a median CR of 23.3 months, with several patients in remission for over three years. The median duration across all treated AML patients (N=9) is 20.1 months.
Trial displays improved survival outcomes vs. standard treatment
When compared with real-world historical data, INB-100 demonstrated significantly higher survival rates:
INB-100:
All patients – 90.9% PFS and OS of 100% at one-year; and
AML patients – 100% PFS and OS of 100% at one-year.
Historical controls in AML:
Center for International Blood and Marrow Transplant Research (CIBMTR) demonstrate a PFS of 67.8% and OS of 74.7% at one-year; and
Kansas University Cancer Center (KUCC) PFS of 57.4% and OS of 66.7% at one-year.
Results demonstrate activity even with older, high-risk patients receiving reduced intensity conditioning (RIC)
Relapse is the most significant challenge leading to mortality for patients undergoing HSCT.
Many of the patients enrolled in the study were older (median age = 68), had complex, high-risk disease or had failed multiple prior therapies, including CAR-T treatments, yet they achieved durable, long-term remission with manageable side effects.
Therapy appears to be well-tolerated without significantly impacting patient Quality of Life
No cytokine release syndrome (CRS) or neurotoxicity; (ICANs)
Tolerable graft-versus-host disease (GvHD) in-line with historical data that is managed with steroids; and
Limited, mild infections.
Dr. Joseph P. McGuirk, Schutte-Speas Professor of Hematology-Oncology, Division Director, Hematologic Malignancies and Cellular Therapeutics Medical Director, Blood and Marrow Transplant, The University of Kansas Cancer Center, commented, "These data suggest that the addition of allogeneic INB-100 gamma-delta T cells appears to have the potential to support durable relapse-free remissions in high-risk leukemia patients, with 100% of treated AML patients remaining in remission after a median follow-up of almost two years post-transplant. Typically, patients receiving reduced-intensity conditioning face substantial risks of relapse within a year, and those who relapse are often left with very few treatment options. INB-100 is not only helping patients avoid this common relapse timeline but is doing so while helping to preserve their quality of life. These results are truly exciting. We are seeing something we rarely encounter in high-risk leukemia patients: sustained, durable remissions with minimal side effects to date. These continued results of INB-100, with the manageable toxicity profile, suggest it could become an attractive cellular therapy with the potential to extend survival in this difficult-to-treat patient population."

William Ho, Chief Executive Officer and co-founder of IN8bio, added, "We’re incredibly pleased with our efforts to continue to deliver consistent, long-term remission results with INB-100. It’s rare to see 100% relapse-free survival in high-risk AML patients, especially over a prolonged period. For patients who may not have had a clear path forward in the past, INB-100 is providing hope, extending survival, and demonstrating the potential to change the standard-of-care. What makes this even more exciting is the safety profile we’ve observed. Gamma-delta T cells are showing that they can do the job of fighting residual cancer cells without causing significant side effects like CRS or neurotoxicity—issues that often plague other cell therapies. As we continue to enroll patients and expand the trial network, we are working diligently to lay the groundwork for the future regulatory pathway towards a potential registrational trial. The IN8bio team is working hard to de-risk the future path to approval and to bring this innovative therapy towards broader patient access. We are committed to providing further updates later this year as we build momentum toward this goal."

Conference Call Details

IN8bio will host a conference call and webcast today, Tuesday, February 11, 2025, at 8:30 am ET. The webcast can be accessed by clicking this link and can also be accessed on the Events & Presentations page of the Company’s website. To participate in the live call, please register using this link. It is recommended that participants register at least 5 minutes in advance of the call. Once registered, participants will be informed of the dial-in number and will be provided a unique PIN.

For more information about the study – including detailed findings, conclusions and next steps – please visit the Company’s poster being presented at the American Society of Transplantation and Cellular Therapy conference: View Source