On November 6, 2024 Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) reported results for the quarter ended September 30, 2024 (Press release, Teva, NOV 6, 2024, View Source [SID1234647832]).

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Mr. Richard Francis, Teva’s President and CEO, said, "The third quarter of 2024 marks our seventh consecutive quarter of growth, with global revenues reaching $4.3 billion, an increase of 15% in local currency terms compared to the third quarter of 2023. Our innovative portfolio and generics business drove strong performance in the third quarter of 2024, reflecting the successful execution of our Pivot to Growth Strategy. Due to our effort and commitment, we are consistently delivering on our growth strategy, executing on our ambitious targets by following our strategic framework, as we remain laser focused on its four key pillars."

Mr. Francis continued, "I am confident that with our newly accelerated innovative pipeline, both early- and late-stage, we are well-positioned to provide meaningful access to medicines for patients who need them, while also delivering continued growth for our shareholders.

"With these strong results, we are raising our 2024 financial outlook, including on revenues, Adjusted EBITDA, and Non-GAAP EPS."

Pivot to Growth Strategy

In May 2023, we introduced our "Pivot to Growth" strategy, which is based on four key pillars: (i) delivering on our growth engines, mainly AUSTEDO, AJOVY, UZEDY and our late-stage pipeline of biosimilars; (ii) stepping up innovation through delivering on our late-stage innovative pipeline assets as well as building up our early-stage pipeline organically and potentially through business development activities; (iii) sustaining our generics medicines powerhouse with a global commercial footprint, focused portfolio, pipeline and manufacturing footprint; and (iv) focusing our business by optimizing our portfolio and global manufacturing footprint to enable strategic capital deployment to accelerate our near and long-term growth engines and reorganizing certain of our business units to a more optimal structure, while also reorganizing key business units to enhance operational efficiency.

Third Quarter 2024 Consolidated Results

The data presented in this press release with respect to operating income (loss), income (loss) before income taxes, income taxes (benefit), net income (loss) attributable to Teva and earnings (loss) per share for prior period has been revised to reflect a revision in relation to a contingent consideration and related expenses. For additional information, see note 1b to our consolidated financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2023 and note 1c to our consolidated financial statements included in our Quarterly Report on Form 10-Q for the period ended September 30, 2024.

Revenues in the third quarter of 2024 were $4,332 million, an increase of 13% in U.S. dollars or 15% in local currency terms, compared to the third quarter of 2023. This increase was mainly due to higher revenues from generic products in all our segments, from AUSTEDO in our United States segment and from sale of product rights in our Europe and International Markets segments.

Exchange rate movements during the third quarter of 2024, including hedging effects, negatively impacted revenues by $88 million, compared to the third quarter of 2023.

Gross profit in the third quarter of 2024 was $2,148 million, an increase of 16% compared to $1,851 million in the third quarter of 2023. Gross profit margin was 49.6% in the third quarter of 2024, compared to 48.1% in the third quarter of 2023. Non-GAAP gross profit was $2,327 million in in the third quarter of 2024, an increase of 13% compared to $2,060 million in the third quarter of 2023. Non-GAAP gross profit margin was 53.7% in the third quarter of 2024, compared to 53.5% in the third quarter of 2023. The increase in both gross profit margin and non-GAAP gross profit margin was mainly due to a favorable mix of products, primarily AUSTEDO, partially offset by a negative impact from foreign exchange rate movements including hedging effects.

Research and Development (R&D) expenses, net in the third quarter of 2024 were $240 million, a decrease of 5% compared to $253 million in the third quarter of 2023. Our lower R&D expenses, net in the third quarter of 2024 were largely driven by reimbursements from our strategic partnerships, reflecting a decrease related to our late-stage innovative pipeline, partially offset by an increase in R&D expenses relating to immunology projects. As we continue to execute on our Pivot to Growth strategy, we see a higher R&D spend in some of our late-stage innovative pipeline assets.

Selling and Marketing (S&M) expenses in the third quarter of 2024 were $626 million, an increase of 9% compared to the third quarter of 2023. This increase was mainly to support revenue growth in generic products, AUSTEDO and AJOVY.

General and Administrative (G&A) expenses in the third quarter of 2024 were $298 million, an increase of 11% compared to the third quarter of 2023.

Other income in the third quarter of 2024 was $21 million, compared to $9 million in the third quarter of 2023. Other income in the third quarter of 2024 included a capital gain from the sale of a business in our International Markets segment.

Operating loss in the third quarter of 2024 was $51 million, compared to an operating income of $344 million in the third quarter of 2023. Operating loss as a percentage of revenues was 1.2% in the third quarter of 2024, compared to an operating income as a percentage of revenues 8.9% in the third quarter of 2023. This decrease was mainly due to a goodwill impairment charge and higher legal settlements and loss contingencies, partially offset by higher gross profit during the third quarter of 2024. Non-GAAP operating income in the third quarter of 2024 was $1,214 million representing a non-GAAP operating margin of 28.0% compared to non-GAAP operating income of $1,020 million representing a non-GAAP operating margin of 26.5% in the third quarter of 2023. The increase in non-GAAP operating margin in the third quarter of 2024 was mainly due to lower operating expenses as a percentage of revenues.

Exchange rate movements during the third quarter of 2024, including hedging effects, negatively impacted our operating loss by $57 million and non-GAAP operating income by $58 million compared to the third quarter of 2023.

Financial expenses, net in the third quarter of 2024 were $272 million, mainly comprised of net-interest expenses of $225 million and a negative exchange rate impact driven mainly from currencies which we were unable to hedge. In the third quarter of 2023, financial expenses, net were $280 million, mainly comprised of net-interest expenses of $247 million and a negative exchange rate impact driven mainly from currencies which we were unable to hedge.

In the third quarter of 2024, we recognized a tax expense of $69 million, on a pre-tax loss of $324 million. In the third quarter of 2023, we recognized a tax benefit of $12 million, on a pre-tax income of $64 million. Our tax rate for the third quarter of 2024 was mainly impacted by impairment charges with no corresponding tax effects, an adjustment to Teva’s corporate tax rate in Israel on losses related to non-qualified tax incentive activities in Israel, legal expenses with no corresponding tax effect related to the fine issued by the European Commission in connection with its antitrust investigation into COPAXONE, and recording of valuation allowance with respect to certain carry over credits outside of Israel. Teva’s tax rate for the third quarter for 2023 was mainly affected by deferred tax benefits resulting from intellectual property related integration plans, which have been adopted, among others, in an effort of addressing the global adoption of the Organization for Economic Co-operation and Development (OECD) Pillar Two minimum effective corporate tax.

Non-GAAP tax rate in the third quarter of 2024 was 16.0%, compared to 9.0% in the third quarter of 2023. Our non-GAAP tax rate in the third quarter of 2024 was mainly impacted by the generation of profits in various jurisdictions with different tax rates, an adjustment to Teva’s corporate tax rate in Israel on losses related to non-qualified tax incentive activities in Israel, recording of valuation allowance with respect to certain carry over credits outside of Israel, as well as infrequent or non-recurring items. Our non-GAAP tax rate in the third quarter of 2023 was mainly impacted by the generation of profits in various jurisdictions with different tax rates, tax benefits, deferred tax benefits resulting from intellectual property related integration plans, as well as infrequent or non-recurring items.

We expect our annual non-GAAP tax rate for 2024 to be between 14%-17%, slightly higher than our non-GAAP tax rate for 2023, which was 13%, mainly due to a lower net tax benefit related to deferred tax assets resulting from intellectual property-related integration plans in 2023.

Net loss attributable to Teva and loss per share in the third quarter of 2024were $437 million and $0.39, respectively, compared to net income attributable to Teva and diluted earnings per share $69 million and $0.06, respectively, in the third quarter of 2023. This decrease was mainly due to the changes in operating (income) loss discussed above.

Non-GAAP net income attributable to Teva and non-GAAP diluted earnings per share in the third quarter of 2024 were $798 million and $0.69, respectively, compared to $677 million and $0.60, respectively, in the third quarter of 2023.

Adjusted EBITDA was $1,327 million in the third quarter of 2024, an increase of 17%, compared to $1,134 million in the third quarter of 2023.

As of September 30, 2024 and 2023, the fully diluted share count for purposes of calculating our market capitalization was approximately 1,167 million shares and 1,157 million shares, respectively.

Non-GAAP information: net non-GAAP adjustments in the third quarter of 2024 were $1,235 million. Non-GAAP net income attributable to Teva and non-GAAP diluted EPS for the third quarter of 2024 were adjusted to exclude the following items:

Amortization of purchased intangible assets of $146 million, of which $136 million is included in cost of sales and the remaining $10 million in S&M expenses;
An adjustment to impairment of long-lived assets in an amount of $51 million;
Goodwill impairment charge of $600 million related to the Teva’s API reporting unit;
Legal settlements and loss contingencies of $450 million mainly related to a provision of $350 million recorded in connection with a decision by the European Commission in its antitrust investigation into COPAXONE (which we intend to appeal), and to an update to the estimated settlement provision of $121 million for the opioid cases (mainly related to the settlement agreement with the city of Baltimore and the effect of the passage of time on the net present value of the discounted payments);
Contingent consideration expenses of $34million;
Equity compensation expenses of $29 million;
Restructuring expenses of $21 million;
Financial expenses of $11 million;
Gain on sale of business of $20 million;
Other non-GAAP items of 56 million;
Items attributable to non-controlling interests of $41 million; and
Corresponding tax effects and unusual tax items of $83 million
We believe that excluding such items facilitates investors’ understanding of our business including underlying performance trends, thereby improving the comparability of our business performance results between reporting periods.

For a reconciliation of the U.S. GAAP results to the adjusted non-GAAP figures and for additional information, see the tables below and the information included under "Non-GAAP Financial Measures." Investors should consider non-GAAP financial measures in addition to, and not as replacement for, or superior to, measures of financial performance prepared in accordance with GAAP.

Cash flow generated from operating activities during the third quarter of 2024 was $693 million, compared to $5 million in the third quarter of 2023. The higher cash flow generated from operating activities in the third quarter of 2024 resulted mainly from higher profit in our United States segment, as well as changes in working capital items, including a positive impact from accounts receivables, net of SR&A, and from accounts payables and inventory levels, partially offset by higher legal payments during the third quarter of 2024.

During the third quarter of 2024, we generated free cash flow of $922 million, which we define as comprising $693 million in cash flow generated from operating activities, $339 million in beneficial interest collected in exchange for securitized accounts receivables (under our EU securitization program), and $38 million in divestitures of businesses and other assets, partially offset by $148 million in cash used for capital investment. During the third quarter of 2023, we generated free cash flow of $229 million, which we define as comprising $5 million in cash flow generated from operating activities, $362 million in beneficial interest collected in exchange for securitized accounts receivables (under our EU securitization program), and $10 million in proceeds from divestitures of businesses and other assets, partially offset by $149 million in cash used for capital investment. The increase in the third quarter of 2024 resulted mainly from higher cash flow generated from operating activities.

As of September 30, 2024, our debt was $18,980 million, compared to $19,833 million as of December 31, 2023. This decrease was mainly due to repayment at maturity of $956 million of 6% senior notes due in 2024, partially offset by $88 million of exchange rate fluctuations. The portion of total debt classified as short-term as of September 30, 2024 was 14% compared to 8% as of December 31, 2023.

Our average debt maturity was approximately 5.5 years as of September 30, 2024, compared to 6.0 years as of December 31, 2023.

Segment Results for the Third Quarter of 2024

United States Segment

As part of a recent shift in executive management responsibilities and in line with our Pivot to Growth strategy, commencing January 1, 2024, Canada is reported as part of our International Markets segment. Prior period amounts were recast to reflect this change.

The following table presents revenues, expenses and profit for our United States segment for the three months ended September 30, 2024 and 2023:

Three months ended September 30,

2024

2023

(U.S. $ in millions / % of Segment Revenues)

Revenues

$

2,225

100%

$

1,896

100%

Gross profit

1,265

56.9%

1,060

55.9%

R&D expenses

151

6.8%

156

8.2%

S&M expenses

259

11.6%

243

12.8%

G&A expenses

107

4.8%

93

4.9%

Other loss (income)

§

§

(2)

§

Segment profit*

$

748

33.6%

$

571

30.1%

* Segment profit does not include amortization and certain other items.
§ Represents an amount less than $0.5 million or 0.5%, as applicable.

Revenues from our United States segment in the third quarter of 2024 were $2,225 million, an increase of $329 million, or 17%, compared to the third quarter of 2023. This increase was mainly due to higher revenues from generic products, AUSTEDO and UZEDY, partially offset by lower revenues from certain innovative products, primarily COPAXONE and BENDEKA and TREANDA.

Revenues by Major Products and Activities

The following table presents revenues for our United States segment by major products and activities for the three months ended September 30, 2024 and 2023:

Three months ended
September 30,

Percentage
Change

2024

2023

2024-2023

(U.S. $ in millions)

Generic products

$

1,094

$

839

30%

AJOVY

58

56

4%

AUSTEDO

435

339

28%

BENDEKA and TREANDA

40

56

(28%)

COPAXONE

69

98

(30%)

UZEDY

35

2

N/A

Anda

380

367

3%

Other

115

140

(18%)

Total

$

2,225

$

1,896

17%

Generic products revenues in our United States segment (including biosimilars) in the third quarter of 2024 were $1,094 million, an increase of 30% compared to the third quarter of 2023, the majority of which was driven by higher revenues from lenalidomide capsules (the generic version of Revlimid), and the remaining, primarily by the launch of liraglutide injection 1.8mg (an authorized generic of Victoza) and higher revenues from epinephrine injectable solution (the generic equivalent of EpiPen and EpiPen Jr).

Among the most significant generic products we sold in the United States in the third quarter of 2024 were lenalidomide capsules (the generic version of Revlimid), epinephrine injectable solution (the generic equivalent of EpiPen and EpiPen Jr), Truxima (the biosimilar to Rituxan) and liraglutide 1.8 mg injection (an authorized generic of Victoza). In the third quarter of 2024, our total prescriptions were approximately 292 million (based on trailing twelve months), representing 7.6% of total U.S. generic prescriptions, compared to approximately 320 million (based on trailing twelve months), representing 8.4% of total U.S. generic prescriptions in the third quarter of 2023, all according to IQVIA data.

On October 1, 2024, Teva launched octreotide acetate for injectable suspension, the first generic version of Sandostatin LAR Depot. Octreotide acetate for injectable suspension is indicated for the treatment of acromegaly and severe diarrhea associated with carcinoid syndrome, and is available to patients in the U.S.

AJOVY revenues in our United States segment in the third quarter of 2024 were $58 million, an increase of 4% compared to the third quarter of 2023, mainly due to growth in volume. In the third quarter of 2024, AJOVY’s exit market share in the United States in terms of total number of prescriptions was 29.1% compared to 24.9% in the third quarter of 2023.

AUSTEDO revenues in our United States segment in the third quarter of 2024 increased by 28% to $435 million, compared to $339 million in the third quarter of 2023, mainly due to growth in volume and expanded access for patients.

AUSTEDO XR (deutetrabenazine) extended-release tablets was approved by the FDA on February 17, 2023, in three doses of 6, 12 and 24 mg, and became commercially available in the U.S. in May 2023. In May 2024, the FDA approved AUSTEDO XR as a one pill, once-daily treatment option in doses of 30, 36, 42, and 48 mg. In July 2024, the FDA approved the 18 mg dosage for AUSTEDO XR, making it a one pill, once-daily option for all available doses. AUSTEDO XR is a once-daily formulation indicated in adults for tardive dyskinesia and chorea associated with Huntington’s disease, which is additional to the currently marketed twice-daily AUSTEDO. AUSTEDO XR is protected by 11 Orange Book patents expiring between 2031 and 2041.

UZEDY (risperidone) extended-release injectable suspension revenues in our United States segment in the third quarter of 2024 were $35 million. UZEDY was approved by the FDA on April 28, 2023 for the treatment of schizophrenia in adults, and was launched in the U.S. in May 2023. UZEDY is a subcutaneous, long-acting formulation of risperidone that controls the steady release of risperidone. UZEDY is protected by nine Orange Book patents expiring between 2025 and 2033. We are moving forward with plans to launch UZEDY in other countries around the world. UZEDY faces competition from multiple other products.

BENDEKA and TREANDA combined revenues in our United States segment in the third quarter of 2024 were $40 million, a decrease of 28% compared to the third quarter of 2023, mainly due to competition from alternative therapies, as well as the entry of generic bendamustine products into the market. The orphan drug exclusivity that had attached to bendamustine products expired in December 2022.

COPAXONE revenues in our United States segment in the third quarter of 2024 were $69 million, a decrease of 30% compared to the third quarter of 2023, mainly due to market share erosion and competition.

Anda revenues from third-party products in our United States segment in the third quarter of 2024 increased by 3% to $380 million, compared to $367 million in the third quarter of 2023, mainly due to higher volumes. Anda, our distribution business in the United States, distributes generic and innovative medicines and OTC pharmaceutical products from Teva and various third-party manufacturers to independent retail pharmacies, pharmacy retail chains, hospitals and physician offices in the United States. Anda is able to compete in the distribution market by maintaining a broad portfolio of products, competitive pricing and delivery throughout the United States.

United States Gross Profit

Gross profit from our United States segment in the third quarter of 2024 was $1,265 million, an increase of 19%, compared to $1,060 million in the third quarter of 2023.

Gross profit margin for our United States segment in the third quarter of 2024 increased to 56.9%, compared to 55.9% in the third quarter of 2023. This increase was mainly due to a favorable mix of products primarily driven by higher revenues from lenalidomide capsules (the generic version of Revlimid) and AUSTEDO.

United States Profit

Profit from our United States segment consists of gross profit less R&D expenses, S&M expenses, G&A expenses and any other income related to this segment. Segment profit does not include amortization and certain other items.

Profit from our United States segment in the third quarter of 2024 was $748 million, an increase of 31% compared to $571 million in the third quarter of 2023. This increase was mainly due to higher gross profit, partially offset by higher S&M and G&A expenses, as discussed above.

Europe Segment

Our Europe segment includes the European Union, the United Kingdom and certain other European countries.

The following table presents revenues, expenses and profit for our Europe segment for the three months ended September 30, 2024 and 2023:

Three months ended September 30,

2024

2023

(U.S. $ in millions / % of Segment Revenues)

Revenues

$

1,265

100%

$

1,146

100%

Gross profit

698

55.2%

648

56.6%

R&D expenses

55

4.3%

62

5.4%

S&M expenses

203

16.0%

184

16.0%

G&A expenses

67

5.3%

66

5.7%

Other loss (income)

1

§

§

§

Segment profit*

$

373

29.5%

$

338

29.5%

___________

* Segment profit does not include amortization and certain other items.
§ Represents an amount less than $0.5 million or 0.5%, as applicable.

Revenues from our Europe segment in the third quarter of 2024 were $1,265 million, an increase of 10%, or $119 million, compared to the third quarter of 2023. In local currency terms, revenues increased by 11% compared to the third quarter of 2023, mainly due to higher revenues from generic and OTC products as well as from AJOVY. Our higher revenues in the third quarter of 2024 were also partly driven by the sale of certain product rights.

In the third quarter of 2024, revenues were negatively impacted by exchange rate fluctuations of $6 million, net of hedging effects, compared to the third quarter of 2023. Revenues in the third quarter of 2024, included $10 million from a negative hedging impact, which is included in "Other" in the table below. Revenues in the third quarter of 2023 included $15 million from a positive hedging impact, which is included in "Other" in the table below.

On November 6, 2024 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported that the Company will present the clinical data of zevorcabtagene autoleucel, CT071, and CT0590 as posters at the 66th Annual Congress of the American Society of Hematology (ASH) (Free ASH Whitepaper) ("ASH") which is due to take place between Dec 7 – 10, 2024 (Press release, Carsgen Therapeutics, NOV 6, 2024, View Source [SID1234647861]). The abstracts are available on ASH (Free ASH Whitepaper) official website.

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"CARsgen is advancing therapeutic options for hematologic malignancies with robust CAR T-cell pipeline, which includes the autologous CAR T-cell therapy zevor-cel, the single-day-culture CT071, and the allogeneic CAR T-cell candidate CT0590. These initiatives underscore CARsgen’s strong commitment to innovation in hematology. Leveraging proprietary technology platforms such as CARcelerate and THANK-uCAR, CARsgen is focused on developing differentiated CAR T-cell therapies to address the critical challenges faced by the clinical community. We are excited to share new data and are confident in the potential of our CAR T-cell therapies to benefit patients worldwide," said Raffaele Baffa, M.D., Ph.D., Chief Medical Officer of CARsgen Therapeutics.

Subgroup Analyses of Phase 2 Study: Evaluating the Efficacy of Fully Human BCMA-Targeting CAR T Cells (Zevorcabtagene Autoleucel) in Patients with Relapsed/Refractory Multiple Myeloma

Publication Number: 4762
Presentation Time: 6:00 PM – 8:00 PM, Monday, December 9, 2024 (PST)

In 102 patients with RRMM who had received at least 3 prior lines of therapy including an immunomodulatory drug and a proteasome inhibitor, the objective response rate (ORR) was 92.2%, the stringent complete response (sCR) or complete response (CR) was 71.6%. The ORR or the CR/sCR rate was not affected by any of the baseline characteristics tested. With a median follow-up of 20.3 (range: 0.4 to 27) months, the median duration of response (DOR), progression-free survival (PFS), and overall survival (OS) data were not mature and therefore, 18-month (18m) and estimated 30-month (30m) event free rates were used as efficacy outcomes for subgroup analyses. The DOR, PFS and OS were not impacted by age or ISS.

These subgroup analyses indicate that baseline characteristics have minimal impact on the clinical efficacy of zevorcabtagene autoleucel, demonstrating that even RRMM patients with poor prognostic factors can benefit from zevorcabtagene autoleucel.

GPRC5D-Targeted CAR T-Cell Therapy CT071 for the Treatment of Refractory/Relapsed Multiple Myeloma

Publication Number: 3451
Presentation Time: 6:00 PM – 8:00 PM, Sunday, December 8, 2024 (PST)

CT071 is a fully human GPRC5D-targeting autologous CAR T-cell product manufactured using an expedited CARcelerate platform which shortens the manufacturing process to around 30 hours resulting in shorter vein-to-vein time. Patients with RRMM who had previously received ≥ 3 prior lines of therapy (LOT) or patients who experienced progression or lack of response having been treated with a proteasome inhibitor and an immunomodulatory agent or those who were double class-refractory, all with ECOG score of 0-2 were enrolled. In 17 patients who had been dosed with CT071, 11 patients (64.7%) experienced cytokine release syndrome (CRS), all at Grade 1 (n=8) or 2 (n=3). No immune effector cell-associated neurotoxicity syndrome (ICANS) was observed. No dose limiting toxicity (DLT) occurred.

The overall response rate (ORR) was 94.1% (16/17), and the stringent complete response (sCR) rate was 52.9% (9/17). Notably, 7 patients achieved complete response or better at week 4. All 4 patients with previous exposure to BCMA or BCMA/CD19 CAR T responded to CT071 (2 with sCR and 2 with partial response).

A First-in-Human Study of CT0590, a Triple Knock-out, Allogeneic CAR T-Cell Therapy Targeting BCMA and NKG2A, in Subjects with Relapsed/Refractory Multiple Myeloma

Publication Number: 4843
Presentation Time: 6:00 PM – 8:00 PM, Monday, December 9, 2024 (PST)

CT0590 is an allogeneic dual CAR T-cell therapy deploying THANK-uCAR technology that targets both BCMA and NKG2A (a membrane protein expressed in NK and T cells), featuring a triple knockout for TRAC/B2M/NKG2A which mitigates against graft-versus-host disease (GvHD), host immune rejection and fratricide.

This is a first-in-human (FIH), open-label, single center, phase I study of CT0590 in subjects with RRMM to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of CT0590 (NCT05066022). As of 22-Apr-2024, 5 subjects were enrolled (4 subjects with RRMM and 1 subject with primary plasma cell leukemia [pPCL] under compassionate use).

No ≥ 3 grade cytokine release syndrome (CRS) was observed. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) or GvHD were observed. No dose limiting toxicities were reported and there were no withdrawal from the study or deaths due to adverse events.

With a median follow-up time of 16.6 months (range: 5.1, 24.2), 3 subjects achieved confirmed responses including 2 subjects with stringent complete response (sCR) and 1 subject with partial response (PR). The 2 subjects with sCR include1 RRMM subject [sCR ongoing] with a DOR longer than 23 months as of data cut-off date and 1 pPCL subject with a duration of response (DOR) of 20 months. In the 2 subjects with sCR, CAR copies peaked at > 280,000 copies/µg genomic DNA.

Preliminary results of this FIH study of the CT0590 allogeneic CAR T-cell therapy demonstrated a manageable safety profile while achieving deep and durable clinical responses.

About Zevorcabtagene Autoleucel

Zevorcabtagene autoleucel is a fully human, autologous BCMA CAR T-cell product for the treatment of Multiple Myeloma (MM). Zevorcabtagene autoleucel was approved by the NMPA on February 23, 2024 for the treatment of adult patients with R/R MM who have progressed after at least 3 prior lines of therapy (including a proteasome inhibitor and an immunomodulatory agent). CARsgen is conducting a separate Phase 1b/2 LUMMICAR STUDY 2 clinical trial in North America to evaluate the safety and efficacy of zevorcabtagene autoleucel in R/R MM.

Zevorcabtagene autoleucel received Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations from the U.S. FDA in 2019, as well as Priority Medicines (PRIME) and Orphan Medicinal Product designations from the European Medicines Agency (EMA) in 2019 and 2020, respectively.

About CT071

CT071 is a CAR T-cell therapy candidate developed utilizing the proprietary CARcelerate platform of CARsgen targeting GPRC5D for the treatment of relapsed/refractory MM or relapsed/refractory plasma cell leukemia (PCL). An IIT (NCT05838131) is ongoing in China to evaluate the preliminary safety and efficacy of CT071 for the treatment of patients with relapsed/refractory multiple myeloma or plasma cell leukemia. A separate investigator-initiated trial (NCT06407947) is ongoing in China for the treatment of patients with newly diagnosed multiple myeloma (NDMM).

About CT0590

CT0590 is a BCMA-targeting allogeneic CAR T-cell product candidate deploying CARsgen’s THANK-uCAR technology. An IIT is ongoing in China to evaluate the preliminary safety and efficacy of CT0590 for the treatment of R/R MM.

On November 6, 2024 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for patients with cancer, reported financial results for the third quarter ended September 30, 2024, and provided a pipeline update on its clinical-stage investigational molecules – targeting TIGIT, HIF-2a, CD73, the A2a/A2b receptors, CD-39, AXL and PD-1 – across multiple common cancers (Press release, Arcus Biosciences, NOV 6, 2024, View Source [SID1234647801]).

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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

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"Through the course of this year, we have presented multiple compelling datasets at medical conferences that we believe have de-risked several programs and support potential best-in-class profiles for our molecules, including our HIF-2a inhibitor casdatifan in ccRCC and our Fc-silent anti-TIGIT antibody domvanalimab in lung and upper gastrointestinal cancers," said Terry Rosen, Ph.D., chief executive officer of Arcus. "Meanwhile, in addition to our rapidly approaching first Phase 3 readout for domvanalimab in gastric cancer, we are aggressively pursuing our development plan for casdatifan, including in the IO-naive ccRCC setting in collaboration with AstraZeneca, and in the post-IO setting with the initiation of our Phase 3 PEAK-1 study in the first half of next year."
Corporate Updates:

•In October 2024, Arcus announced a clinical collaboration with AstraZeneca to evaluate casdatifan in combination with volrustomig, AstraZeneca’s investigational PD-1/CTLA-4 bispecific antibody, in IO-naive patients with ccRCC. AstraZeneca will operationalize the study. This is the second clinical collaboration between Arcus and AstraZeneca. Gilead retains the right to opt in to the development and commercialization for casdatifan after delivery of a qualifying data package.
Pipeline Highlights:

Casdatifan (HIF-2a inhibitor)
Casdatifan Updates:
•First clinical data from the casdatifan 100mg and 50mg expansion cohorts of ARC-20, a Phase 1/1b study in metastatic ccRCC, were presented in an oral plenary session at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium in October. Observations from the 100mg daily expansion cohort included:
◦An objective response rate (ORR) of 34% (2 responses are pending confirmation; 25% confirmed ORR), a low rate of primary progression of 19% and a high disease control rate of 81%.
◦The median progression-free survival (PFS) had not been reached at the time of the data cutoff.

◦Together, these data support the potential for casdatifan to be a best-in-class HIF-2a inhibitor for the treatment of ccRCC.
•In the third quarter, Arcus had a successful Type B meeting with the U.S. Federal Drug Administration (FDA) to discuss its first Phase 3 study for casdatifan, PEAK-1, which will evaluate casdatifan in combination with cabozantinib versus cabozantinib in post-IO patients with ccRCC. Arcus is moving rapidly toward the initiation of PEAK-1 in the first half of 2025.
Upcoming Casdatifan Milestones:
•Multiple expansion cohorts of ARC-20 evaluating casdatifan in ccRCC as a monotherapy and in combination with cabozantinib in ccRCC are underway with additional data presentations expected in the next 12 months.
◦100mg (50mg twice daily (BID), capsules) and 50mg expansion cohorts: Updated data, including median PFS, are expected to be presented in the first quarter of 2025.
◦150mg and 100mg (once daily (QD), tablets) expansion cohorts: Initial data are expected to be presented in 2025.
◦100mg of casdatifan plus cabozantinib: Safety data are expected to be presented in 2025.
Domvanalimab (Fc-silent anti-TIGIT antibody) plus Zimberelimab (anti-PD-1 antibody)
Domvanalimab-Zimberelimab Updates:
•Data from Part 1 of ARC-10, a randomized study evaluating domvanalimab plus zimberelimab in PD-L-1 high NSCLC are being presented at the SITC (Free SITC Whitepaper) Annual Meeting in November.
•Domvanalimab plus zimberelimab was associated with greater PFS, overall survival, and objective response rate compared with zimberelimab or chemotherapy.
◦A 36% reduction in risk of death (hazard ratio [HR]=0.64) was observed for domvanalimab plus zimberelimab compared to that of zimberelimab alone.
◦Zimberelimab reached a median overall survival of 2 years, and the median overall survival for domvanalimab plus zimberelimab was not reached.
◦Treatment-related adverse events leading to treatment discontinuation were low (10.5%) for the combination of domvanalimab and zimberelimab.
•Data from an investigator-sponsored trial evaluating domvanalimab plus zimberelimab in anti-PD-(L)1 refractory hepatocellular carcinoma will be presented in an oral session at the SITC (Free SITC Whitepaper) Annual Meeting.
Upcoming Domvanalimab-Zimberelimab Milestones:
•Overall survival data from the Phase 2 EDGE-Gastric study, evaluating domvanalimab plus zimberelimab and chemotherapy in upper gastrointestinal (GI) adenocarcinomas, are expected to be presented in 2025.

CD73-Adenosine Axis: Quemliclustat (small-molecule CD73 inhibitor) and Etrumadenant (A2a/A2b receptor antagonist)

Quemliclustat
•Arcus has initiated PRISM-1, a Phase 3 trial of quemliclustat combined with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in pancreatic cancer.
Etrumadenant
•Biomarker data from cohort B of ARC-9, a randomized Phase 1b/2 study evaluating etrumadenant plus zimberelimab, FOLFOX chemotherapy and bevacizumab (EZFB) versus regorafenib in third-line metastatic colorectal cancer (mCRC), are being presented at SITC (Free SITC Whitepaper) in November.

Early Clinical Programs

•Evaluation of AB801, a potent and highly selective small-molecule AXL inhibitor, in the dose-escalation phase of a Phase 1/1b study in patients is ongoing. Arcus anticipates advancing this molecule into expansion cohorts in NSCLC in early 2025.
Financial Results for Third Quarter 2024:
•Cash, Cash Equivalents and Marketable Securities were $1.1 billion as of September 30, 2024, compared to $866 million as of December 31, 2023. The increase during the period is primarily due to the receipt of $320 million in cash from Gilead for their January 2024 equity investment, the receipt of the $100 million option continuation payment from Gilead in July 2024 and proceeds from our $50 million term loan, partially offset by the use of cash in research and development activities. We believe our cash, cash equivalents and marketable securities on-hand will be sufficient to fund operations into mid-2027. Cash, cash equivalents and marketable securities are expected to be between $950 million and $985 million at the end of 2024.
•Revenues were $48 million for the third quarter 2024, compared to $32 million for the same period in 2023. In the third quarter 2024, Arcus recognized $41 million in license and development services revenue related to the advancement of programs and Taiho’s exercise of its option for the license of quemliclustat for the Taiho Territory of $15 million, as well as $7 million in other collaboration revenue primarily related to Gilead’s ongoing rights to access Arcus’s research and development pipeline in accordance with the Gilead collaboration agreement.
•Research and Development (R&D) Expenses were $123 million for the third quarter 2024, compared to $82 million for the same period in 2023. The net increase of $41 million was primarily driven by higher clinical trial and headcount-related costs associated with our late-stage development program activities. Non-cash stock-based compensation expense was $9 million for the third quarter 2024, compared to $8 million for the same period in 2023. For the third quarter 2024 and 2023, Arcus recognized gross reimbursements of $37 million and $33 million, respectively, for shared expenses from its collaborations, primarily the Gilead collaboration. R&D expense by quarter may fluctuate due to the timing of clinical manufacturing and standard-of-care therapeutic purchases with a corresponding impact on reimbursements.
•General and Administrative (G&A) Expenses were flat for the third quarter 2024, compared to the same period in 2023. Non-cash stock-based compensation expense was $10 million for each of the third quarter 2024 and 2023.
•Net Loss was $92 million for the third quarter 2024, compared to $71 million for the same period in 2023.
Conference Call Information:
Arcus will host a conference call and webcast today, November 6, at 2:00 PM PT / 5:00 PM ET to discuss its third-quarter 2024 financial results and pipeline updates. To access the call, please dial +1 (404) 975-4839 (local) or +1 (833) 470-1428 (toll-free), using Access Code: 940081. Participants may also register for the call online using the following link: View Source;confId=72838. To access the live webcast and accompanying slide presentation, please visit the "Investors & Media" section of the Arcus Biosciences website at www.arcusbio.com. A replay of the webcast will be available following the live event.
Arcus Ongoing and Announced Clinical Studies:
Trial Name Arms Setting Status NCT No.
Lung Cancer
STAR-121 dom + zim + chemo vs. pembro + chemo 1L NSCLC (PD-L1 all-comers) Ongoing Registrational Phase 3
NCT05502237
PACIFIC-8 dom + durva vs. durva Unresectable Stage 3 NSCLC Ongoing Registrational Phase 3
NCT05211895
ARC-7 zim vs. dom + zim vs. etruma + dom + zim 1L NSCLC (PD-L1 ≥ 50%) Ongoing Randomized Phase 2
NCT04262856
EDGE-Lung dom +/- zim +/- quemli +/- chemo 1L/2L NSCLC (lung cancer platform study) Ongoing Randomized Phase 2
NCT05676931
VELOCITY-Lung
dom +/- zim +/- etruma +/- sacituzumab govitecan-hziy or other combos
1L/2L NSCLC (lung cancer platform study) Ongoing Randomized Phase 2
NCT05633667
Upper Gastrointestinal Cancers
STAR-221 dom + zim + chemo vs. nivo + chemo 1L Gastric, GEJ and EAC Ongoing Registrational Phase 3
NCT05568095
EDGE-Gastric (ARC-21) dom +/- zim +/- quemli +/- chemo 1L/2L Upper GI Malignancies
Ongoing
Randomized Phase 2
NCT05329766
Colorectal Cancer

ARC-9 etruma + zim + mFOLFOX vs. SOC 2L/3L/3L+ CRC
Ongoing
Randomized Phase 2
NCT04660812
Pancreatic Cancer
PRISM-1 quemli + gem/nab-pac vs. gem/nab-pac 1L PDAC Ongoing Phase 3
NCT06608927
ARC-8 quemli + zim + gem/nab-pac vs. quemli + gem/nab-pac 1L, 2L PDAC Ongoing Randomized Phase 1/1b
NCT04104672
Kidney Cancer
PEAK-1 cas + cabo vs. cabo Post-IO ccRCC Planned Phase 3 TBD
ARC-20 cas, cas + cabo Cancer Patients / ccRCC Ongoing Phase 1/1b
NCT05536141
Other
ARC-25 AB598 Advanced Malignancies Ongoing
NCT05891171
ARC-27 AB801 Advanced Malignancies Ongoing
NCT06120075

cabo: cabozantinib; cas: casdatifan; dom: domvanalimab; durva: durvalumab; etruma: etrumadenant; gem/nab-pac: gemcitabine/nab-paclitaxel; nivo: nivolumab; pembro: pembrolizumab; quemli: quemliclustat; SOC: standard of care; zim: zimberelimab; ccRCC: clear cell renal cell carcinoma; CRC: colorectal cancer; EAC: esophageal adenocarcinoma; GEJ: gastroesophageal junction; GI: gastrointestinal; NSCLC: non-small cell lung cancer; PDAC: pancreatic ductal adenocarcinoma.

On November 6, 2024 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, reported its financial results for the third quarter ended September 30, 2024 and provided a business update (Press release, Immunocore, NOV 6, 2024, View Source [SID1234647817]).

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"We are proud to report another strong quarter, marking two years of continuous growth for KIMMTRAK and another quarter of positive net income," said Bahija Jallal, Immunocore’s Chief Executive Officer. "We are also making significant strides in advancing our broad pipeline – with brenetafusp in oncology, the HIV functional cure trial in infectious diseases, and in autoimmune diseases with tissue-targeted programs for type 1 diabetes and dermatologic diseases."

"KIMMTRAK’s 28% growth over Q3 last year is driven by higher demand in the United States and Germany and by expanded patient reach with 11 launches this year," said Ralph Torbay, Immunocore’s Chief Commercial Officer. "We are excited about the potential to bring KIMMTRAK to more patients with melanoma through the Phase 3 TEBE-AM trial that is expected to complete enrollment in early 2026, and the Phase 3 ATOM trial that is planned to start randomization this quarter."

Third Quarter 2024 Highlights (including post-period)

KIMMTRAK
The Company’s lead product, KIMMTRAK, is approved in 38 countries and has been launched in 21 countries globally to date for HLA-A*02:01 positive patients with unresectable or metastatic uveal melanoma (mUM). KIMMTRAK continues to be the standard of care in most markets where it is launched. The Company sees three key growth areas for KIMMTRAK: continued expansion in mUM, the potential expansion into 2L+ advanced cutaneous melanoma and adjuvant uveal melanoma.

Metastatic uveal melanoma

KIMMTRAK net product sales were $80.2 million and $225.9 million for the three and nine months ended September 30, 2024, respectively, representing increases of 28% and 32% respectively, compared to the prior year periods.
Growth in the US and Germany was driven by increased demand based on continued community penetration and growing duration of treatment.
New baseline blood gene expression signature data was presented at the European Society for Medical Oncology 2024 Meeting (ESMO 2024) confirming that T cell fitness in blood is an important parameter of clinical activity for KIMMTRAK in previously treated uveal melanoma.

2L+ previously treated cutaneous melanoma

Randomization continues in the registrational Phase 3 trial (TEBE-AM), which includes three arms – KIMMTRAK monotherapy, KIMMTRAK in combination with pembrolizumab, and control. The Company expects to complete randomization in the first half of 2026.
The TEBE-AM Phase 3 trial in 2L+ cutaneous melanoma has a primary endpoint of overall survival.
Adjuvant uveal (or ocular) melanoma

Randomization in the ATOM Phase 3 trial, led by the European Organisation for Research and Treatment of Cancer (EORTC), is on track to start in the fourth quarter of 2024.
ATOM is currently the only active registrational Phase 3 trial in adjuvant uveal melanoma.
PRAME
Brenetafusp (IMC-F106C) is the Company’s lead PRAME-A02 ImmTAC bispecific candidate. Brenetafusp is being evaluated in combination with nivolumab, in a Phase 3 registrational trial (PRISM-MEL-301) in patients with first-line advanced cutaneous melanoma and in a Phase 1/2 clinical trial, as monotherapy and in combination, across multiple tumor types, including ovarian, non-small cell lung (NSCLC), and endometrial carcinoma.

PRISM-MEL-301 – First PRAME Phase 3 clinical trial with brenetafusp in first-line advanced or metastatic HLA-A*02:01 positive cutaneous melanoma

Ongoing randomization of patients in PRISM-MEL-301 in multiple countries.
Trial is evaluating brenetafusp + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab.
Phase 1/2 clinical trial of brenetafusp (PRAME-A02) in multiple solid tumors

Clinical data presented at ESMO (Free ESMO Whitepaper) 2024 from the Phase 1 trial in patients with heavily pre-treated platinum-resistant high grade serous ovarian cancer showed signals of activity in heavily pretreated, platinum resistant patients. Disease control rate was 58% in monotherapy patients and 69% for combination patients. Overall survival (OS) was still maturing (73% 6-months OS rate in the monotherapy cohort). ctDNA molecular response rate was 31% and 82%, respectively, in the monotherapy and combination cohorts, associated with longer progression free survival and OS. Brenetafusp is well tolerated as monotherapy and in combination with gemcitabine, nab-paclitaxel and pegylated doxorubicin.
Data presented at ESMO (Free ESMO Whitepaper) 2024 showed peripheral blood T cell fitness signature is an important parameter of brenetafusp clinical activity in ovarian cancer and uveal melanoma.
The Company is currently evaluating brenetafusp in combination with non-platinum chemotherapies in platinum resistant ovarian cancer and with bevacizumab and with platinum chemotherapy in earlier lines of platinum sensitive ovarian cancer.
The Company continues signal detection for brenetafusp in metastatic non-small-cell lung cancer cohorts, including in combination with docetaxel and with osimertinib in earlier-line NSCLC. As a result, the Company will not release initial data in the fourth quarter of 2024.
IMC-P115C (PRAME-A02 Half-Life Extended) & IMC-T119C (PRAME-A24)

On track for first patient to be treated in the Phase 1 trial with IMC-P115C in first half of 2025.

Additional Oncology Candidates

IMC-R117C (first PIWIL1-A02 targeted immunotherapy) for colorectal and other gastrointestinal cancers
The Company has leveraged its proprietary peptidomic database to validate a novel target, PIWIL1. PIWIL1 is a negative prognostic marker and is expressed across a range of tumors including colorectal, which is historically insensitive to immune checkpoints, as well as gastro-esophageal, and pancreatic cancer.

Remain on track to treat the first patient in the Phase 1/2 trial of IMC-R117C in the fourth quarter of 2024.
The Phase 1/2 trial will assess the safety and clinical activity of IMC-R117C, as a monotherapy and in combination with standards of care, in colorectal and other gastrointestinal cancers.
ImmTAV candidates for a functional cure in infectious diseases
The Company’s bispecific TCR technology platform has potential to offer a new approach for the treatment of chronic infections and aims to eliminate evidence of remaining virus in circulation after the patient stops taking medication – known as a "functional cure". Two investigational candidates are in Phase 1 clinical trials for people living with human immunodeficiency virus (HIV) and people with chronic Hepatitis B infection (HBV).

Phase 1 trial of IMC-M113V (Gag-A02) for people living with HIV

The objective of the clinical trial is to identify a safe and tolerable dose and evaluate whether IMC-M113V could lead to reduction in the viral reservoir and, after stopping antiretroviral therapies and IMC-M113V, delay or prevent HIV rebound.
A biologically active dose in the multiple ascending dose (MAD) portion of the trial has been reached and the Company is enrolling more people living with HIV to characterize anti-viral activity and to explore higher doses with data expected in the first quarter of 2025.
Phase 1 trial of IMC-I109V (Envelope-A02) for people living with HBV

Expect to complete the single ascending dose (SAD) portion of the trial in the fourth quarter of 2024.

Tissue-specific down modulation of the immune system for autoimmune diseases
The Company is expanding its platform into autoimmune diseases with two new, first-in-class bispecific candidates recently entering its pipeline. The key differentiator of the Company’s ImmTAAI (Immune Modulating Monoclonal TCRs Against AutoImmune disease) platform is tissue-specific down modulation of the immune system whereby, when tethered to the tissue of interest, the new candidates suppress pathogenic T cells via PD1 receptor agonism.

IMC-S118AI (pre-pro insulin A02 x PD1), intended for disease-modifying treatment in type 1 diabetes

IMC-S118AI recognizes a peptide from pre-proinsulin presented by HLA-A02 on beta cells, coupled with a PD1 agonist effector arm.

Undisclosed non-HLA restricted (universal) candidate for inflammatory dermatological diseases

The candidate is an antigen presenting cell (APC) tethered ImmTAAI and is not HLA restricted (i.e. universal for all populations).

Corporate Updates

In August, Chief Financial Officer (CFO) and Head of Strategy, Brian Di Donato, informed the Company of his plans to leave at the end of the year, to take the role of Chief Executive Officer at a private, early-stage biotech headquartered in San Diego, California. The Company is progressing in its search for a new CFO. Brian will remain as the Company’s CFO and Head of Strategy through the end of 2024, to ensure a smooth transition.

Financial Results

For the third quarter ended September 30, 2024, the Company generated net product sales of $80.2 million compared to $62.6 million for the same period in 2023. This increase was due to revenue from KIMMTRAK, of which $57.3 million was in the United States, $21.0 million in Europe, and $1.9 million in international regions. The increase in net product sales was due primarily to increased volume in the United States and global country expansion, as the Company continued its commercialization efforts.

For the third quarter ended September 30, 2024, research and development (R&D) expenses were $52.8 million, compared to $43.2 million for the same period in 2023. This increase was primarily driven by expenses incurred for the tebentafusp programs, including the Phase 3 trials: TEBE-AM in previously treated advanced cutaneous melanoma and ATOM in adjuvant uveal melanoma.

For the quarter ended September 30, 2024, SG&A expenses were $35.5 million, compared to $35.5 million for the same period in 2023.

Basic and diluted earnings per share was $0.17 for the quarter ended September 30, 2024, as compared to a basic and diluted earnings per share of $0.02 for the same period in 2023. Net income for the quarter ended September 30, 2024 was $8.7 million, as compared to $0.9 million for the same period in 2023.

Cash, cash equivalents, and marketable securities at September 30, 2024 were $901.3 million. The Company plans to use existing cash to repay its $50 million loan by the end of 2024 and also expects to pay approximately $40 million in sales-related rebate accruals in the fourth quarter of 2024.

About ImmTAC molecules for cancer

Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune "cold" low mutation rate tumors.

About ImmTAV molecules and infectious diseases

ImmTAV (Immune mobilizing monoclonal TCRs Against Virus) molecules are novel bispecifics that are designed to enable the immune system to recognize and eliminate virally infected cells.
Immunocore is advancing clinical candidates to achieve functional cure for patients with HIV and hepatitis B virus (HBV). The Company aims to achieve sustained control of HIV after patients stop anti-retroviral therapy (ART), without the risk of virological relapse or onward transmission. This is known as ‘functional cure’. For the treatment of HBV, the Company aims to achieve sustained loss of circulating viral antigens and markers of viral replication after stopping medication for people living with chronic HBV.

About ImmTAAITM molecules and autoimmune diseases

ImmTAAI (Immune mobilizing monoclonal TCRs Against AutoImmune disease) molecules are novel bispecifics that are designed for tissue-specific down modulation of the immune system. When tethered to the tissue of interest, ImmTAAI candidates suppress pathogenic T cells via PD1 receptor agonism. The Company is currently advancing two candidates for autoimmune diseases, including type 1 diabetes and inflammatory dermatological diseases.

About PRISM-MEL-301 (NCT06112314) – Phase 3 trial with brenetafusp (IMC-F106C, PRAME-A02) in 1L advanced cutaneous melanoma

The Phase 3 registrational trial is randomizing HLA-A*02:01-positive patients with previously untreated advanced melanoma, to brenetafusp + nivolumab versus nivolumab or nivolumab + relatlimab, depending on the country where the patient is enrolled. The trial will initially randomize to three arms: two brenetafusp dose regimens (40 mcg and 160 mcg) and a control arm. One of the two brenetafusp dose regimens will be discontinued after an initial review of the first 60 patients randomized to the two experimental arms (90 patients randomized total). The primary endpoint of the trial is progression free survival (PFS) by blinded independent central review (BICR), with secondary endpoints of overall survival (OS) and overall response rate (ORR).

About the IMC-F106C-101 Phase 1/2 trial

IMC-F106C-101 is a first-in-human, Phase 1/2 dose escalation trial in patients with multiple solid tumors, including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), endometrial, ovarian, cutaneous melanoma, and breast cancers. The Phase 1 dose escalation trial was designed to determine the maximum tolerated dose (MTD), as well as to evaluate the safety, preliminary anti-tumor activity and pharmacokinetics of IMC-F106C (brenetafusp), a bispecific protein built on Immunocore’s ImmTAC technology, and the Company’s first molecule to target the PRAME antigen. The Company is enrolling patients into three expansion arms in NSCLC, as well as ovarian and endometrial carcinomas. The IMC-F106C-101 trial is adaptive and includes the option for Phase 2 expansion, allowing for approximately 100 patients treated per tumor type in the Phase 1 and 2 expansion arms. Dose escalation continues in additional solid tumors as well as plans for combination arms with standards-of-care, including checkpoint inhibitors, chemotherapy, and tebentafusp.

About TEBE-AM – Phase 3 registrational trial with tebentafusp in previously treated advanced cutaneous melanoma

The trial is randomizing patients with second-line or later advanced cutaneous melanoma who have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a BRAF kinase inhibitor. Patients are randomized to one of three arms, including tebentafusp – as monotherapy or in combination with an anti-PD1 – or a control arm. The primary endpoint is overall survival.

About the ATOM Phase 3 trial – Phase 3 registrational trial with tebentafusp in adjuvant uveal melanoma

The EORTC-led Phase 3 clinical trial will include sites in 10 EU countries and the United States and will randomize HLA-A*02:01-positive patients with high-risk primary uveal melanoma after definitive treatment, by surgery or radiotherapy, and no evidence of metastatic disease on imaging. The trial is expected to enroll a total of 290 patients who will be randomized 1:1 to one of two arms: tebentafusp as monotherapy or observation. The primary endpoint of the trial is relapse-free survival (RFS), with secondary objectives of overall survival and safety and tolerability of tebentafusp. Exploratory objectives include comparison of health-related quality of life between the treatment arms and evaluation of the role of circulating tumor DNA (ctDNA) as a biomarker for the presence of residual disease.

About Uveal Melanoma

Uveal melanoma is a rare and aggressive form of melanoma affecting the eye. Although it is the most common primary intraocular malignancy in adults, the diagnosis is rare, and up to 50% of people with uveal melanoma will eventually develop metastatic disease. Unresectable or metastatic uveal melanoma typically has a poor prognosis and had no approved treatment until KIMMTRAK.

About Cutaneous Melanoma

Cutaneous melanoma (CM) is the most common form of melanoma. It is the most aggressive skin carcinoma and is associated with the vast majority of skin cancer-related mortality. The majority of patients with CM are diagnosed before metastasis but survival remains poor for the large proportion of patients with metastatic disease. Despite recent progress in advanced melanoma therapy, there is still an unmet need for new therapies that improve first-line response rates and duration of response as well as for patients who are refractory to first-line treatments.

About KIMMTRAK

KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform, designed to redirect and activate T cells to recognize and kill tumor cells. KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom.

IMPORTANT SAFETY INFORMATION

Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS occurred in 89% of patients who received KIMMTRAK, with 0.8% being grade 3 or 4. Ensure immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS.

Skin Reactions

Skin reactions, including rash, pruritus, and cutaneous edema occurred in 91% of patients treated with KIMMTRAK. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions.

Elevated Liver Enzymes

Elevations in liver enzymes occurred in 65% of patients treated with KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.

Embryo-Fetal Toxicity

KIMMTRAK may cause fetal harm. Advise pregnant patients of potential risk to the fetus and patients of reproductive potential to use effective contraception during treatment with KIMMTRAK and 1 week after the last dose.

The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate.

For more information, please see full Summary of Product Characteristics (SmPC) or full U.S. Prescribing Information (including BOXED WARNING for CRS).

On November 5, 2024 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported financial results for the third quarter ended September 30, 2024, and provided an overview of recent developments (Press release, UroGen Pharma, NOV 6, 2024, View Source [SID1234647833]).

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"The recent FDA acceptance of our New Drug Application for UGN-102 marks a significant milestone in our mission to deliver breakthrough treatments to patients," said Liz Barrett, President and Chief Executive Officer of UroGen. "Supported by robust clinical evidence, we believe UGN-102 has the potential to redefine the treatment of low-grade intermediate-risk non-muscle invasive bladder cancer and provide longer treatment-free intervals for patients that currently face the burden of repetitive surgeries under general anesthesia. We look forward to a potential FDA approval by the PDUFA target action date of June 13, 2025. If approved, we believe UGN-102 will represent a paradigm shift in care, addressing a total market opportunity of over $5 billion. Our team is fully focused on preparing for a successful commercial launch of UGN-102, if approved, in 2025."

Q3 2024 and Recent Business Highlights:

UGN-102 (mitomycin) for intravesical solution:

In October 2024, the U.S. Food and Drug Administration (FDA) accepted UroGen’s New Drug Application (NDA) for investigational drug UGN-102 (mitomycin) for intravesical solution as a treatment for low-grade intermediate risk non-muscle invasive bladder cancer (LG-IR-NMIBC). The FDA granted a Prescription Drug User Fee Act (PDUFA) target action date of June 13, 2025.
The NDA for UGN-102 is supported by a comprehensive development program which demonstrated a clinically meaningful complete response rate and a strong duration of response across three late phase clinical trials and an acceptable safety profile. The Phase 3 ENVISION trial successfully met its primary endpoint by demonstrating that patients treated with UGN-102 had a 79.6% (95% CI, 73.9%, 84.5%) complete response (CR) rate at three months following the first instillation of UGN-102. More recently, durability data from ENVISION showed that UGN-102 demonstrated an 82.3% (95% CI, 75.9%, 87.1%) 12-month duration of response (DOR) by Kaplan-Meier estimate in patients who had achieved a complete response at three months after the first instillation of UGN-102. This is the highest DOR ever reported in this patient population. The ENVISION trial demonstrated that UGN-102 has an acceptable safety profile that is consistent with the side effect profile observed in previous clinical trials.
JELMYTO (mitomycin) for pyelocalyceal solution in low-grade upper tract urothelial cancer (LG-UTUC):

Generated net product revenue of $25.2 million in the third quarter of 2024, compared to $20.9 million in the third quarter of 2023, primarily driven by strong underlying demand growth and also reflecting non-patient purchases.
Next-generation novel mitomycin-based formulation for urothelial cancers

In October 2024, the first patient was dosed in the Phase 3 UTOPIA clinical trial of investigational drug UGN-103 (mitomycin) for intravesical solution in patients with LG-IR-NMIBC. UGN-103 is a next generation product that combines UroGen’s RTGel technology with a novel mitomycin formulation licensed from medac GmbH. UGN-103 is planned to follow the potential FDA approval and launch of UGN-102 for LG-IR-NMIBC. UroGen plans to initiate a Phase 3 study early next year to explore the safety and efficacy of UGN-104, its next generation product for the treatment of LG-UTUC. To learn more about the UTOPIA trial, refer to clinicaltrials.gov/NCT06331299.
In September 2024, UroGen received a Notice of Allowance from the United States Patent and Trademark Office for a patent application covering, among other things, the use of UGN-103 in the treatment of LG-IR-NMIBC. The U.S. patent, once issued, will have an expiration date in December 2041.
Corporate

In October 2024, UroGen appointed Chris Degnan as Chief Financial Officer. Mr. Degnan brings broad expertise in financial strategy, investor relations, SEC reporting, accounting and compliance, having previously held CFO roles at Galera Therapeutics and Verrica Pharmaceuticals. He replaced Don Kim who left the Company to pursue other opportunities.
Third Quarter 2024 Financial Results

JELMYTO Revenue: JELMYTO net product revenues were $25.2 million and $20.9 million for the three months ended September 30, 2024, and 2023, respectively.

R&D Expense: Research and development expenses for the third quarter of 2024 were $11.4 million, including non-cash share-based compensation expense of $0.6 million as compared to $10.2 million, including non-cash share-based compensation expense of $0.4 million, for the same period in 2023.

SG&A Expense: Selling, general and administrative expenses for the third quarter of 2024 were $28.9 million, including non-cash share-based compensation expense of $2.9 million. This compares to $21.8 million, including non-cash share-based compensation expense of $1.8 million, for the same period in 2023.

Financing on Prepaid Forward Obligation: UroGen reported non-cash financing expense related to the prepaid forward obligation to RTW Investments of $5.9 million in the third quarter of 2024, compared to $5.5 million in the same period in 2023.

Interest Expense on Long-Term Debt: Interest expense related to the outstanding $125 million term loan facility with funds managed by Pharmakon Advisors was $2.7 million in the third quarter of 2024, compared to $3.8 million in the same period in 2023.

Net Loss: UroGen reported a net loss of $23.7 million or ($0.55) per basic and diluted share in the third quarter of 2024 compared with a net loss of $21.9 million or ($0.68) per basic and diluted share in the same period in 2023.

Cash & Cash Equivalents: As of September 30, 2024, cash, cash equivalents and marketable securities totaled $254.2 million.

For further details on the Company’s financials, including results for the 9-month period ended September 30, 2024, refer to Form 10-Q, filed with the SEC.

2024 Revenue, Operating Expense, and RTW Expense Guidance: With respect to the Company’s previously provided full-year 2024 JELMYTO revenue guidance, the Company expects full-year revenues to be below the low end of the guidance range. The Company does expect JELMYTO to achieve low double-digit year-over-year revenue growth for the full year 2024. With respect to the Company’s previously provided full-year 2024 operating expenses guidance, the Company expects to be toward the midpoint of the guidance range, including non-cash share-based compensation expense of $9 to $13 million, subject to market conditions. The anticipated full year 2024 non-cash financing expense related to the prepaid obligation to RTW Investments is unchanged and expected to be in the range of $21 to $26 million. The rate for the cash component of the RTW obligation will be 13% of global net product sales of JELMYTO in 2024.

Conference Call & Webcast Information: Members of UroGen’s management team will host a live conference call and webcast today at 10:00 AM Eastern Time to review UroGen’s financial results and provide a general business update.

The live webcast can be accessed by visiting the Investors section of the Company’s website at View Source Please connect at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast.