On October 21, 2021 ALX Oncology Holdings Inc., ("ALX Oncology") (Nasdaq: ALXO), a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint pathway, reported the first patient has been dosed in the Phase 1/2 ASPEN-05 study evaluating the combination of evorpacept, a next-generation CD47 blocker, with venetoclax and azacitidine for the treatment of patients with acute myeloid leukemia ("AML") (Press release, ALX Oncology, OCT 21, 2021, View Source [SID1234591867]).

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The Phase 1 portion of the ASPEN-05 study will characterize the safety and confirm the dose of evorpacept in combination with venetoclax and azacitidine in patients with relapsed/refractory AML and previously untreated AML who are not candidates for intensive induction therapy. The Phase 2 portion of the study will evaluate the efficacy of the combination in patients with previously untreated AML who are not candidates for intensive induction therapy.

ASPEN-05 is based on promising preclinical data with evorpacept in combination with venetoclax and azacitidine in non-clinical models of leukemia, as well as clinical data from an ongoing phase 1 study (NCT03013218) evaluating evorpacept in combination with multiple anti-cancer agents in both solid and hematologic malignancies.

"Patients with either relapsed/refractory AML or previously untreated AML who are not considered eligible for intensive induction regimens remain in urgent need of tolerable and effective new therapies," said Harry Erba, M.D., Ph.D., Director of the Leukemia Program at the Duke Cancer Institute. "We are looking forward to evaluating the addition of evorpacept to venetoclax and azacitidine. ALX148 was specifically designed for use in combination to maximize phagocytosis of tumor cells while minimizing the toxicities commonly associated with other CD47-targeted approaches."

"ASPEN-05 builds upon compelling evorpacept combination activity observed in non-clinical models of leukemia. With demonstrated tolerability of evorpacept in multi-agent chemotherapy regimens, we are excited to characterize evorpacept with this standard backbone of AML therapy," said Sophia Randolph, M.D., Ph.D., Chief Medical Officer of ALX Oncology. "Through blockade of the CD47 myeloid checkpoint, evorpacept in combination with venetoclax and azacitidine may potentially transform treatment options for patients with AML."

The ASPEN-05 trial is registered under NCT04755244. ALX Oncology owns worldwide commercial rights to evorpacept.

About Acute Myeloid Leukemia

AML is an aggressive blood cell cancer that can rapidly progress and lead to death if not treated promptly. AML is the most common form of acute leukemia in adults, with an estimated 19,940 new cases and 11,180 deaths from AML in the United States. Due to advanced age and comorbidities at the time of diagnosis, a significant number of patients are not considered eligible for intensive and potentially curative therapies. Despite advances in available care, the estimated 5-year survival for patients in the United States with AML remains only 29%.

On October 21, 2021 Johnson & Johnson and partner Legend Biotech reported that they are expecting an FDA decision for their first CAR-T product, cilta-cel, in November (Press release, Johnson & Johnson, OCT 21, 2021, View Source [SID1234591823]). To prepare for the upcoming launch of the personalized cell therapy, the Big Pharma company is planning a specialized patient support program, a dedicated sales team and more.

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J&J intends to roll out a customized program to help cilta-cel-prescribed multiple myeloma patients navigate the treatment journey, Serge Messerlian, Janssen’s U.S. oncology president, said in a recent interview.

CAR-T therapies modify a patient’s own T cells to make them better weapons against cancer bearing a specific biomarker. For such a personalized medicine, "one needs to be very thoughtful not just [about] the product, but there’s a very important service component to that," Messerlian said.

RELATED: J&J, Legend Biotech’s multiple myeloma CAR-T scores FDA priority review, setting up a clash with BMS’ Abecma

Because of the complexity in production, CAR-T products can be pricey. Before cilta-cel, Bristol Myers Squibb recently introduced a rival BCMA-targeted cell therapy, Abecma, at a list price of $419,500. Patients need to travel to designated treatment centers to have their T cells drawn and later to receive the final product. They must also monitor for a potentially life-threatening side effect known as cytokine release syndrome after treatment.

For J&J’s program, each patient will get one-on-one assistance navigating access challenges and help with the logistics associated with treatment, Messerlian said. For the upcoming launch, J&J is working on CAR-T site initiations and making sure the market is ready to receive the medicine. Although the company already has a popular multiple myeloma therapy, Darzalex, cilta-cel will have a separate sales team, he said.

Building personalized cancer drug support programs
J&J has a separate personalized patient assistance program for Darzalex, called Janssen Compass, which also covers prostate cancer med Erleada. The company is now rolling out Janssen Compass on a national scope after a limited run, Messerlian said.

"Compass is a very patient-centric, patient-oriented platform; it almost serves like a shepherd," Messerlian explained. In Janssen Compass, a single point of contact—a nurse—is assigned to help bring the right resources to a patient to manage obstacles along the way, including access challenges and side effects.

RELATED: J&J cell therapy partner Legend carves out production foothold in Belgium as myeloma drug nears finish line

About half of the patients that get on any drug drop off within six months, Messerlian noted, and not all of them are related to costs.

Sometimes, patients don’t understand what to expect on the treatment journey or fully acknowledge the benefits of the medicine, so they may not be committed to the therapy, Messerlian said. In Janssen Compass, a "care navigator" will help set expectations, educate each patient on how to manage potential obstacles and support them in developing a care plan to communicate with doctors.

Gaining treatment insights to develop better care
In return, J&J is getting valuable insights. Janssen Compass allows the company to "understand and analyze which patients will be most likely to drop off, and what are some interventions we can [use to] predict and prevent … these types of patient drop-offs," Messerlian said.

Beyond patient support, J&J is also teaming up with healthcare facilities and specialty networks to help train doctors, especially in the community setting. The goal of such education is, as Messerlian put it, about "bending the quality-of-life curve."

RELATED: Pharmas’ return on $5B spent yearly on patient support programs? Only 3% are using them: survey

Working with its care partners, J&J is collecting and analyzing data to map out how various patients move through the treatment process, aiming to improve outcomes along the way.

"It comes down to understanding, what are the inputs of this care process, what are the decisions along the process, and can you standardize to that," Messerlian said. "[With] a standard set, you can then roll that out in partnership with other practices to ultimately elevate the standard of care."

On October 21, 2021 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported the signing of a collaboration agreement granting China Resources Double-Crane Pharmaceutical Co., Ltd. (CRDC) exclusive Asia territorial rights to develop a novel investigational oral COVID-19 antiviral therapeutic compound using Ligand’s BEPro technology (Press release, Ligand, OCT 21, 2021, View Source [SID1234591822]). Ligand will receive an upfront payment in respect of the collaboration, and if the program advances, clinical and regulatory milestone payments, and tiered royalties on net sales. CRDC will be responsible for all costs related to the program.

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BEPro is a proprietary prodrug technology that is specifically applicable to nucleotides and nucleotide analogs for the development of compounds with improved product profiles. Ligand has generated preclinical pharmacokinetics data showing its oral BEPro-enabled COVID-19 antivirals to have a favorable blood concentration profile and generate lower levels of active nucleotide in the kidney, a potential site for toxicity, than other oral and intravenous comparators. Ligand has filed multiple patents globally on the BEPro technology and potential antiviral compounds.

"This transaction with CRDC is another deal in a long history of success converting our inventions, data and intellectual property into licenses to advance important medicines and deliver value to our shareholders," said John Higgins, CEO of Ligand Pharmaceuticals. "We are proud of the important work our team has contributed toward addressing the pandemic and are pleased with this new collaboration. China Resources Group is one of the largest Chinese pharmaceutical companies and is looking forward to robust development of this program through their subsidiary CRDC."

On October 21, 2021 Ultimovacs ASA ("Ultimovacs") (OSE ULTI), a clinical-stage leader in immune stimulatory vaccines for cancer, reported its universal cancer vaccine, UV1, in combination with checkpoint inhibitors has received Fast Track designation from the U.S. FDA in the treatment of unresectable or metastatic melanoma – either as add-on therapy to pembrolizumab or as add-on therapy to ipilimumab (Press release, Ultimovacs, OCT 21, 2021, View Source [SID1234591774]). Ultimovacs is currently evaluating UV1 as add-on therapy to ipilimumab and nivolumab as first-line treatment for unresectable or metastatic melanoma in a Phase II study named INITIUM.

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Ultimovacs senior management will host a webcast on the Fast Track designation and the supporting clinical data at 13.00 CET on Thursday October 21.

The FDA Fast Track process is designed to facilitate the development and expedite the review of drugs that meet urgent needs in serious medical conditions. Fast Track designation enables early and frequent communication with the FDA to support the drug’s development, as well as entitlement to a Rolling Review of the Biologic License Application. Drugs with Fast Track designation may also be considered for Accelerated Approval and Priority Review provided certain criteria are met.

"We are delighted UV1 has received the Fast Track designation and look forward to working more closely with the FDA to bring UV1 to melanoma patients as soon as possible," said Carlos de Sousa, Chief Executive Officer of Ultimovacs. "The FDA’s decision recognizes the potential synergy of UV1 and checkpoint inhibitors and will greatly encourage physicians and patients involved in our Phase II clinical trial INITIUM. We remain committed to progressing UV1 in our four ongoing Phase II clinical studies and assessing development of UV1 with pembrolizumab in advanced melanoma."

The Fast Track designation is based on data from two separate Phase I trials of UV1 in combination with checkpoint inhibitors, either with pembrolizumab (anti-PD-1) or with ipilimumab (anti-CTLA-4). According to data disclosed recently, UV1 in combination with pembrolizumab as a first-line treatment in advanced melanoma was shown to be safe with promising early efficacy data; an objective response rate (ORR) of 57% was reached with 30% of patients achieving a complete response (CR), or complete disappearance of their tumors. At 24 months follow up, 80% of patients were alive. In a second cohort, similar levels of tumor destruction were seen with 90% of patients remained alive after one year. Peer-reviewed data published in May 2021 in Frontiers in Immunology demonstrated that UV1 with ipilimumab was safe and showed signals of prolonged efficacy in advanced melanoma, the combination achieving ORR of 33% and 5-year overall survival (OS) rate of 50%.

UV1 is currently being investigated in combination with checkpoint inhibitors in four Phase II trials: in unresectable or metastatic melanoma, ovarian cancer, head and neck squamous cell carcinoma and malignant pleural mesothelioma.

Ultimovacs’ webcast on the Fast Track designation and clinical data at 13.00 CET (7.00 am EST) on Thursday 21 October 2021 will be accessible here and from the company website.

On October 21, 2021 Silence Therapeutics plc (AIM:SLN and Nasdaq: SLN), a leader in the discovery, development and delivery of novel short interfering ribonucleic acid (siRNA) therapeutics for the treatment of diseases with significant unmet medical need, reported it is hosting its R&D Day in New York City (Press release, Silence Therapeutics, OCT 21, 2021, View Source [SID1234591770]).

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During the event, Silence plans to showcase its proprietary mRNAi GOLD platform and current clinical programs, including SLN360 for cardiovascular disease due to high lipoprotein(a), or Lp(a), and SLN124 for thalassemia and myelodysplastic syndrome (MDS) as well as a newly added program in polycythemia vera (PV). Silence will also provide an update on its growing discovery pipeline and plans to deliver 2-3 INDs per year from 2023.

Mark Rothera, President and Chief Executive Officer of Silence Therapeutics, said: "The vision at Silence has always been to build an exquisite platform that would enable the development of longer-lasting precision medicines to transform patients’ lives. We are pleased to report strong progress across both our proprietary and partnered pipelines, including plans to further expand the SLN124 program into a third indication, PV, where endogenous hepcidin modulation can potentially improve outcomes for 3.5 million people worldwide who currently have very limited treatment options. Through our hybrid business model, we are committed to maximizing the substantial opportunity for our mRNAi GOLD platform and remain well positioned to deliver 2-3 INDs per year from 2023."

Giles Campion, MD, EVP, Head of R&D and Chief Medical Officer of Silence Therapeutics, said: "We are very encouraged by the outcomes from our recent safety review committee meeting for SLN360. Based on their recommendations, we have now defined our dose range and are ready to start the multiple-ascending dose study. We are also extending the follow-up period in the single-ascending dose study to fully characterize SLN360’s duration of action, which may be even longer than we initially anticipated. We look forward to further evaluating SLN360 in the clinic and remain on-track to report topline data in the single-ascending dose study in the first quarter of 2022."

mRNAi GOLD Proprietary Program Updates

SLN124 Program
New highlighted updates include:

Plans to pursue new PV indication and start a phase 1 trial in the second half of 2022.
FDA acceptance of the US IND in myelodysplastic syndrome (MDS).
Enrollment continues in the two single-ascending dose studies for thalassemia and MDS. Silence anticipates topline data from both studies in the third quarter of 2022.
Positive results from the healthy volunteer study reported in May 2021 accepted for poster presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held December 11-14, 2021.
SLN360 Program
New highlighted updates include:

On-track to report top-line data in the single-ascending dose study in the first quarter of 2022.
Key outcomes from the independent safety review committee meeting:
Recommendation to extend follow-up period in the single-ascending dose study from 150 days to 365 days to fully assess the duration of action, which may be longer than initially anticipated based on preclinical modelling.
The therapeutic dose range has been established based on Cohorts 1-4 (optional Cohort 5 not needed) and study can now proceed to the multiple-ascending dose phase.
On-track to initiate phase 2 development in the second half of 2022, pending regulatory discussions.

Building Proprietary Pipeline

Advancing two new undisclosed proprietary programs following the Hansoh collaboration announced last week (read full release here). Hansoh has the option to license China region rights at the end of phase 1.

mRNAi GOLD Partnered Program Updates

AstraZeneca Collaboration for Cardiovascular, Renal, Metabolic and Respiratory Diseases

Continuing work with AstraZeneca to develop siRNAs for two undisclosed targets.
On-track to initiate work on five targets within the first three years of the collaboration.
Mallinckrodt Collaboration for Complement-Mediated Diseases

Progressing IND-enabling studies for SLN501 C3-targeting program and expect to initiate a phase 1 study in the first half of 2022.
Developing siRNAs for two other undisclosed complement-mediated disease targets.
Hansoh Collaboration

In addition to the two proprietary programs outlined above, Silence will work with Hansoh on a third undisclosed program which Hansoh has the option to license worldwide at the point of IND filing.
As part of the Hansoh agreement, Hansoh made a $16 million upfront cash payment and Silence has the potential for up to $1.3 billion in additional milestones plus royalties tiered from low double-digit to mid-teens on Hansoh net product sales.
Targeting 2-3 INDs per year from 2023

Silence remains on-track to deliver 2-3 INDs per year from 2023 through both its proprietary and partnered mRNAi GOLD platform programs. Key highlighted updates include:
Expanded translational genomics efforts, contributing both to finding new, genetically validated disease-causing genes and continuously fine-tuning the siRNA design algorithm using machine learning
A fine-tuned drug discovery process
Aiming for a mixed-risk portfolio of validated and novel targets with projects at different stages of drug discovery ensuring multiple shots on goal
The Company’s R&D Day will be held today, October 21, 2021 from 9:00 am to 11:30 am ET at the Convene, 530 Fifth Avenue, in New York City and will include a live video stream.