GSK delivers strong 2023 performance and upgrades growth outlooks

On January 31, 2024 GlaxoSmithKline reported strong 2023 performance and upgrades growth outlooks (Press release, GlaxoSmithKline, JAN 31, 2024, View Source [SID1234639764]).

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Agenus to Participate in Oppenheimer 34th Annual Healthcare Life Sciences Conference

On January 31, 2024 Agenus Inc. ("Agenus") (Nasdaq: AGEN), a leader in discovering and developing novel immunological agents to treat various cancers, reported that Dr. Garo Armen, Chairman and CEO, will participate in a fireside chat and investor one-on-ones at the upcoming Oppenheimer Healthcare Conference on February 13th – 14th (Press release, Agenus, JAN 31, 2024, View Source [SID1234639763]). The fireside chat will take place at 8:00 a.m. ET on February 14th.

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A live webcast and replay of the fireside chat will be accessible on the company’s website at View Source

European Medicines Agency Grants CEL-SCI a Waiver of Strict Pediatric Requirements, Clearing the Path Towards Marketing Authorization for Multikine

On January 31, 2024 CEL-SCI Corporation (NYSE American: CVM) reported that the European Medicines Agency (EMA) Paediatric Committee granted CEL-SCI a product-specific waiver of strict requirements for commercialization of cancer drugs in the European Union (EU) (Press release, Cel-Sci, JAN 31, 2024, View Source [SID1234639762]). According to the opinion letter:

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"The Paediatric Committee, having assessed the waiver application in accordance with Article 13 of Regulation (EC) No 1901/2006 as amended, recommends as set out in the appended summary report:

to grant a product-specific waiver for all subsets of the paediatric population and the above mentioned condition(s) in accordance with Article 11(1)(c) of said Regulation…."
CEL-SCI’s investigational cancer immunotherapy Multikine (Leukocyte Interleukin, Injection)* is intended for newly diagnosed adult (>18 years old) patients with locally advanced resectable primary squamous cell carcinoma of the head and neck (SCCHN).

"The granting of a paediatric investigation plan waiver by the EMA’s Paediatric Committee is a big step forward for Multikine, because it is one less hurdle that we face on our path towards commercialization in Europe, which could have greatly delayed our plans in the EU had the waiver not been granted," said Geert Kersten, CEO of CEL-SCI. "We are moving forward in multiple countries and regulatory jurisdictions at the same time, including not only the US and Europe but also the United Kingdom and Canada."

The EU Paediatric Regulation which came into force in January 2007 dramatically changed the regulatory environment for pediatric medicines in Europe. Its objective is to bolster investigation and development of medicinal products for the paediatric population. The regulation’s main impact was the establishment of the Paediatric Committee (PDCO), which is responsible for coordinating the EMA’s work on medicines for children by determining the studies that companies must carry out as part of paediatric investigation plans (PIPs). A PIP is a development plan aimed at ensuring that the necessary data are obtained through studies in children, to support the authorization of a medicine for children.1, 2

All applications for marketing authorization for new medicines in the EU must include the results of studies as described in an agreed PIP, unless the medicine is exempt because of a deferral or waiver.2 The process of developing an agreed PIP and conducting research on children under a PIP is often lengthy and stringent. Much has been said publicly about these "onerous" requirements and how difficult they can be to navigate.3

A summary of the PIP process can be reviewed by clicking here.

About Multikine

Multikine is designed to help the immune system "target" the tumor at a time when the immune system is still relatively intact and thereby thought to be better able to mount an attack on the tumor. A pivotal Phase 3 study in advanced primary squamous cell carcinoma of the head and neck (oral cavity and soft-palate) was started in early 2011 and was fully enrolled with 928 patients by September 2016, completed follow-up and database-lock occurred in December 2020. To test for an overall survival benefit, the study required CEL-SCI to wait until at least 298 (deaths) events had occurred among the two main comparator groups.

Multikine’s positive clinical outcomes come from the following pathway, which has been definitively proven in our Phase 3 trial:

Multikine causes pre-surgical responses;
Pre-surgical responses lead to longer life;
Therefore, Multikine pre-surgery treatment is associated with achieving longer life.
A "pre-surgical response" is a significant change in disease before surgery, and there were two kinds of responses observed in our Phase 3 trial. First, there were "reductions" in the size of the tumor—a reduction of 30% or more qualified as a "pre-surgical reduction" or "PSR" for short. Second, there were disease "downstages," e.g., the disease improved from Stage IV to Stage III. We call this a "pre-surgical downstaging" or "PSD" for short. Our 2022 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) cancer conference presentation reported on PSR, and our 2023 ESMO (Free ESMO Whitepaper) presentation reported on PSD.

Across the whole Phase 3 trial, PSRs were seen in 8.5% of Multikine patients compared to zero in the control. PSDs were seen in 22% of Multikine patients vs 13% in the control. Because Multikine was the only therapy given to these patients before surgery, we believe the data show that Multikine was the cause of the higher rates of PSR and PSD. These results were seen in the entire Phase 3 study population, not from a subgroup.

The Phase 3 data also showed that patients with pre-surgical responses from Multikine lived far longer than those without Multikine. PSR patients were 72% likely to be alive after five years, whereas control patients were only about 49% likely to be alive after five years. Patients with PSD saw five-year chance of survival of about 68%. These results are also seen in the entire Phase 3 study population, not just in a subgroup. Moreover, they were shown with strong statistical significance with p-values < 0.005. (See Figure 1)

The Phase 3 study showed that Multikine worked best in patients who were deemed "low risk" after surgery, about 40% of the study population. These patients saw a significant 14.1% absolute 5‑year survival benefit vs control. It made sense biologically that these patients would benefit most from Multikine, because they tended to have immune systems that were not yet compromised by the disease. "High risk" patients, by contrast, typically had lymph nodes invaded by the tumor, and needed chemotherapy after surgery. Because their lymph nodes were compromised, this made it harder for their immune systems to work, and they needed surgery as soon as possible without waiting an extra three weeks to administer Multikine.

The Phase 3 study also showed that Multikine was more effective for patients with low PD-L1 tumor expression than for patients with high PD-L1 expression. PD-L1 is a protein receptor on the tumor surface that helps the tumor neutralize the immune system cells that attack the tumor. It makes sense that patients whose tumors express low PD-L1 would be more likely to respond to Multikine, because their tumors have lower defenses against the patient’s immune system. Low PD-L1 tumor expression represented about 70% of the study population.

Targeting low PD-L1 differentiates Multikine from other immunotherapies. For example, checkpoint inhibitors like Keytruda and Opdivo appear to best serve patients having high PD-L1, because these drugs work by blocking PD-1/PD-L1 receptor interaction. While none of these drugs are currently approved as a first-line treatment before surgery, even if such approvals came in the future, the large majority of patients in this group having low PD-L1 would still be expected to need Multikine.

In view of the above Phase 3 clinical evidence, the Multikine target population is directed to patients who present at diagnosis with N0 nodal involvement and also with low PD-L1 tumor expression (defined as tumor proportions score (TPS) < 10). These patients can be readily identified upon diagnosis with tests that physicians routinely use in cancer screening. For instance, a PET scan is used to determine the N0 nodal status and no extracapsular spread, and a screening biopsy is used to determine the low PD-L1 expression. Doctors already routinely screen head and neck cancer patients using PET scans and biopsy. (See Figure 2)

The Phase 3 data shows that Multikine cut the risk of death in half at five years versus the control in the target population. Survival increased from 45% in the control group to 73% in the Multikine group at five years. This means the risk of death fell to 27% in the Multikine group from 55% in the control. (See Figure 3)

Another way to see the survival benefit of Multikine in the target population is the Kaplan-Meier curve from our ESMO (Free ESMO Whitepaper) ’23 poster. (See Figure 4) These results had a low p-value of 0.0015, which is very significant as a statistical matter. These data show yield a low hazard ratio of 0.349, with 95% confidence intervals of 0.18 and 0.66.

Our regulatory strategy going forward is to seek immediate approval of Multikine wherever possible. What drives us forward is the compelling patient need for the pre-surgical responses from Multikine, which translates to much better survival. The patients’ need is paramount to all stakeholders, including regulators, physicians, CEL-SCI and CEL-SCI’s investors.

We believe the benefit-risk balance strongly favors immediate patient access to Multikine. (See Figure 5) An "unmet need" is a factor for approval considered by all major regulatory bodies worldwide. In the Multikine target population, there is also a tremendous unmet need for improved survival. The current standard of care provides only about a 50/50 chance of surviving five years, whereas Multikine could increase that survival rate to over 70% based on the Phase 3 data. Chemotherapy has improved outcomes for some head and neck patients, but chemotherapy is only indicated for high-risk patients, who are not likely to fall within the Multikine target population. Currently available immunotherapies are given after surgery or where surgery is not indicated. In contrast, Multikine is given before surgery to patients with resectable tumors. Available checkpoint inhibitors work best on tumors with high PD-L1 expression, whereas Multikine works best in tumors with low PD-L1 expression. Therefore, Multikine’s target population is underserved, and will continue to be underserved, by current therapies, but Multikine can meet the need for improved survival.

Atara Biotherapeutics and Pierre Fabre Laboratories Announce Publication of Phase 3 ALLELE Tab-cel® Data in The Lancet Oncology

On January 31, 2024 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, and Pierre Fabre Laboratories, a global player in oncology and responsible for worldwide commercialization of tabelecleucel (tab-cel or EBVALLO), reported that data from the pivotal Phase 3 ALLELE study of tab-cel, approved in the European Union in adults and children two years of age and older with relapsed or refractory (r/r) Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD) following solid organ transplant (SOT) or hematopoietic cell transplant (HCT), were published for the first time online in The Lancet Oncology (Press release, Atara Biotherapeutics, JAN 31, 2024, View Source [SID1234639761]).

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The data were published in an article titled, "Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein–Barr virus-positive post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE): a phase 3, multicentre, open-label trial," and can be accessed at the following link: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00649-6/fulltext

"The results of the ALLELE study highlight the clinical value of tab-cel, which is now EMA and MHRA approved, and is being made available to patients in Europe through our partner Pierre Fabre Laboratories as a first-of-its-kind treatment for those with a devastating disease that previously had limited treatment options," said Pascal Touchon, President and Chief Executive Officer of Atara. "As we prepare for our tab-cel BLA submission in the second quarter 2024, we look forward to interacting with the FDA to progress towards approval based on our robust clinical data."

As reported in The Lancet Oncology publication, the ALLELE study met its primary endpoint. 22 of 43 EBV+ PTLD patients achieved an objective response (51.2% objective response rate, or ORR). Those that responded to tab-cel had longer survival, with an estimated one-year overall survival of 84.4% (95% CI: 58.9, 94.7) for responders versus 34.8% (95% CI: 14.6, 56.1) for non-responders. The median duration of response was 23.0 months and the median overall survival was 18.4 months. Tab-cel was well tolerated with no reports of tumor flare reaction, cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome, and no events of graft-versus-host disease or SOT rejection as related to tab-cel. These interim data were previously presented at the 2022 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

These pivotal trial data are supported by a recent updated analysis from the October 2023 data cut of the ongoing ALLELE study that continued to demonstrate a statistically significant 49% ORR (p<0.0001), consistent durability of response, estimated OS, and favorable safety profile in the intended population for the proposed U.S. label. ln addition, real-world results from the multicenter Expanded Access Program study in Europe demonstrated an ORR of 66.7% in 24 EBV+ PTLD patients and were presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

"Patients with relapsed or refractory EBV+ PTLD have limited treatment options and poor overall survival measured in only weeks to months," said Susan Prockop, MD, lead investigator, Boston Children’s Hospital-Dana Farber Cancer Institute. "These clinically meaningful data reinforce the life-saving potential of tabelecleucel for these patients, for whom there are no approved therapies in the U.S. and helps address an urgent unmet medical need."

Tab-cel was granted marketing authorization under the brand name EBVALLO in December 2022 by the European Commission (EC) as a monotherapy for the treatment of adult and pediatric patients two years of age and older with r/r EBV+ PTLD who have received at least one prior therapy. For solid organ transplant patients, prior therapy includes chemotherapy unless chemotherapy is inappropriate. In the United States, Atara plans to submit a biologics license application (BLA) to the U.S. Food and Drug Administration for tab-cel for the treatment of EBV+ PTLD in the second quarter of 2024. Additionally, in December 2023, Atara reported the first results from the ongoing Phase 2 EBVision trial, which has the potential to further extend the clinical experience and potential of tab-cel into broader indications.

In December 2023, Atara announced the closing of the expanded global partnership with Pierre Fabre Laboratories for the U.S. and remaining global commercial markets for tabelecleucel, building on an initial partnership covering Europe, Middle East, Africa, and other select emerging markets.

"Current results from the first global, multicenter, open-label Phase 3 study of the new allogeneic T-cell therapy, tabelecleucel, show significant clinical benefit and a favorable safety profile in a severely affected population. These results bring a lot of hope for patients, and confirm the innovative nature of this treatment, also recognized through the Prix Galien prize that we received in France. With the recent EU marketing authorization, EBVALLO is the first EBV-specific allogeneic T-cell therapy available for patients with r/r EBV+ PTLD after HCT or SOT and their families. All this resonates perfectly with our purpose ‘every time we care for a single person, we make the whole world better,’" said Núria Perez-Cullell, Director of Medical Affairs, Patients & Consumers at Pierre Fabre Laboratories.

Takeda Announces Third-Quarter FY2023 Results; On-Track Towards Full-Year Management Guidance With Strong Momentum in Growth & Launch Products

On January 31, 2024 Takeda (TOKYO:4502/NYSE:TAK) reported financial results for the third quarter of fiscal year 2023 (period ended December 31, 2023) (Press release, Takeda, JAN 31, 2024, View Source [SID1234639760]). With year-to-date strong momentum in its Growth & Launch Products (+12.7% at CER) offsetting the significant revenue impact of generic entrants, Takeda remains on track towards its full-year Management Guidance.

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Takeda chief financial officer, Costa Saroukos, commented:
"In FY2023 Q3 we made further progress in our vision to discover and deliver life-transforming treatments, receiving two new U.S. FDA approvals and broadening the reach of our existing portfolio with multiple life-cycle management approvals for our Growth & Launch Products.

"We remain on track towards our full-year Management Guidance at CER, reflecting significant generic impact, lower coronavirus vaccines revenue and investment in R&D and data, digital and technology to secure our long-term competitiveness, as well as continued strong momentum in our Growth & Launch Products.

"We continue to improve our debt profile with 100% of our debt now at fixed interest rates averaging 1.6%, and our financial foundation remains strong as we enter the fourth quarter of FY2023."

FINANCIAL HIGHLIGHTS

Results for FY2023 Q3 YTD Ended December 31, 2023

(Billion yen,
except
percentages and
per share
amounts)

REPORTED

CORE(c)

(Non-IFRS)(a)

FY2023 Q3 YTD

vs. PRIOR YEAR

(Actual % change)

FY2023 Q3 YTD

vs. PRIOR YEAR

(Actual % change)

vs. PRIOR YEAR

(CER % change(d))

Revenue

3,212.9

+4.6%

3,212.9

+4.6%

+0.0%

Operating Profit

224.1

-44.2%

865.6

-9.3%

-12.7%

Margin

7.0%

-6.1pp

26.9%

-4.1pp

Net Profit

147.1

-48.6%

643.6

-9.0%

-12.2%

EPS (yen)

94

-48.9%

412

-9.7%

-12.9%

Operating Cash Flow

437.8

-36.0%

Free Cash Flow
(Non-IFRS)(a)(b)

36.3

-93.8%

(a) Further information regarding certain of Takeda’s Non-IFRS measures is posted on Takeda’s investor relations website at View Source." target="_blank" title="View Source." rel="nofollow">View Source

(b) We define Free Cash Flow as cash flows from operating activities, subtracting acquisition of property, plant and equipment ("PP&E"), intangible assets and investments as well as removing any other cash that is not available to Takeda’s immediate or general business use, and adding proceeds from sales of PP&E, as well as from sales of investments and businesses, net of cash and cash equivalents divested.

(c) Core results adjust our reported results calculated and presented pursuant to IFRS to exclude the effect of items unrelated to Takeda’s core operations, such as, to the extent applicable for each line item, non-recurring items, purchase accounting effects and transaction related costs, as well as amortization and impairment of intangible assets and other operating income and expenses.

(d) CER (Constant Exchange Rate) change eliminates the effect of foreign exchange rates from year-over-year comparisons by translating Reported or Core results for the current period using corresponding exchange rates in the same period of the previous fiscal year.

FY2023 OUTLOOK

On track towards full-year FY2023 Management Guidance

(Billion yen except per share amounts)

FY2023

FORECAST
(Unchanged from

October 2023)

FY2023

MANAGEMENT GUIDANCE

Core Change at CER (Non-IFRS)
(Unchanged from May 2023)

Revenue

3,980.0

Core Revenue

3,980.0

Low-single-digit % decline

Reported Operating Profit

225.0

Core Operating Profit

1,015.0

Low-10s % decline

Reported Net Profit

93.0

Reported EPS (yen)

59

Core EPS (yen)

447

Low-20s % decline

Free Cash Flow*

400.0-500.0

Annual Dividend per Share (yen)

188

*Free Cash Flow forecast reflects expenditures related to the acquisition of TAK-279 from Nimbus and in-licensing of FRUZAQLA (fruquintinib) from HUTCHMED.

Additional Information About Takeda’s FY2023 Q3 Earnings Results
For more details on Takeda’s FY2023 Q3 results and other financial information, including key assumptions in FY2023 forecast and management guidance, please visit: View Source

For more information on Takeda’s commercial progress across the five key business areas and pipeline updates, please visit: View Source