Member Info for Energyshares

This shows how difficult it is to develop effective new treatment options in first-line therapy for advanced STS and that a doxorubicin-based regimen continuous to be the gold-standard even more than 40 years after its introduction into the treatment armamentarium.

Have little AIM listed Avacta
finally found a replacement for the Gold Standard.

Keep hold of those Golden Tickets GLA….

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457009/#:~:text=Doxorubicin%2Dbased%20chemotherapy%20remains%20as,therapy%20in%20several%20STS%20subtypes.

FDA approval. PTE is designed to restore some of the patent term "lost" during the FDA's review process.

Congress provided for PTE as part of the Drug Price Competition and Patent Term Restoration Act of 1984, PL 98-417, S 1538 98 Stat. 1585 (the "Hatch-Waxman Act").Congressional records show that PTE was one piece of a carefully calibrated scheme to weigh incentives for innovation and market competition for drugs. Congress enacted PTE in part to:

"restore . . . some of the incentive for innovation which has weakened as Federal pre-market approval requirements have become more expensive and time-consuming. That incentive will produce both the investment and commitment to research [sic] and development that will again place the United States in unquestioned leadership in the field. And it will generate an increase in the number of important new drugs, among the most vital causes for this century's dramatic increase in the length and quality of life."

The statute enables the owners of patents on human drug products, medical devices, food additives, or color additives, and animal drug products to obtain patent term extension for delays at the regulatory agency.

FDA approval PTE 20 years from launch.

DTW
Yes it looks like they can apply for PTE if approved through FDA
"Patent Term Extension" or "PTE."

No wonder Avacta are going down FDA route as priority they can then extend patents to Pre/Cision.

Patent holders have the right to exclude others from making, using, selling, or offering to sell an invention but only during the time a patent is in force. This right disappears upon patent expiration, making the "monopoly" period that a patent is in force an important issue. Patents filed and granted on or after June 8, 1995 typically expire twenty years from the date of the first filing of the patent application ("patent term").
However, the patent term may be modified. Here, we discuss one way of extending patent term called "Patent Term Extension" or "PTE."

“PTE is only available for certain types of patents, most commonly patents related to drug products and medical devices. Patent holders of such patents typically benefit most after the drug or device is commercially launched and competition is excluded”

PTE rights, however, are limited. For example, for a patent that claims the product, PTE only extends exclusive patent rights to any FDA-approved use for the product. Thus, if the patent claims other products (let's call them products B and C) in addition to the approved product (product A), the exclusive patent rights to the other products (products B and C) expire with the original expiration date of the patent.

https://www.fr.com/insights/ip-law-essentials/intro-patent-term-extension/#

Without a change in the law, a patent cannot be extended beyond the term for which it issued. The only way to extend protection is to invent and patent an improvement to the originally patented invention.

So every new indication they patent a new application to extend protection.

https://link.springer.com/article/10.1007/s11192-017-2311-4

Page 5
Substrate exclusively licensed from Tufts University. (Multiple patent families with priority dates 2012/14).

https://avacta.com/wp-content/uploads/2020/06/Placing-Presentation-June-2020-1.pdf

https://avacta.com/wp-content/uploads/2022/10/241022-Avacta-Ltd-Trade-Marks-Summary.pdf

gmcc
Before update there was just four.
Tripled going to America.
Looking good :)

A lot of measures AVA6000 v Doxorubicin

Outcome measure
Maximum drug concentration (Cmax) of AVA6000 & Doxorubicin
Cmax (maximum plasma concentration) of AVA6000 and Doxorubicin after administration after Cycle 1 and 2 for 72 hours post-dose.
Cycle 1 and Cycle 2, 0-72 hours post dose (Dose Escalation)
Area under the concentration versus time curve (AUC) of AVA6000 & Doxorubicin
AUC (Area under the concentration versus time curve) of AVA6000 and Doxorubicin after administration after Cycle 1 and 2 for 72 hours post-dose.
Cycle 1 and Cycle 2, 0-72 hours post dose (Dose Escalation)
Elimination half-life (t1/2) of AVA6000 & Doxorubicin
t1/2 (Elimination half-life) of AVA6000 and Doxorubicin after administration after Cycle 1 and 2 for 72 hours post-dose.
Cycle 1 and Cycle 2, 0-72 hours post dose (Dose Escalation)
Renal clearance (CLr) of AVA6000 & Doxorubicin
CLr (Renal clearance) of AVA6000 and Doxorubicin after administration after Cycle 1 and 2 for 72 hours post-dose.
Cycle 1 and Cycle 2, 0-72 hours post dose (Dose Escalation)
Objective response rate (ORR)
ORR is defined as the proportion of patients achieving a best overall response of confirmed partial responses (PR) or complete response (CR), per Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
Up to one year
Duration of Response (DoR)
DoR is defined as the duration of time from date of first response to date of disease progression, as per RECIST v1.1
Up to one year
Progression-free-survival (PFS)
PFS is defined as the time from the date of the first dose to the date of the first documentation of confirmed disease progression or death, whichever occurs first, as per RECIST v1.1
Up to one year
Overall survival (OS)
Overall survival (OS), defined as the date of first dose) to the occurrence of death from any cause
Up to one year

BV
https://clinicaltrials.gov/ct2/show/NCT04969835

Scroll to very bottom page…

That’s a lot more MeSH terms added thanks gmcc

Additional relevant MeSH terms:
Sarcoma
Biliary Tract Neoplasms
Neoplasms, Unknown Primary
Neoplasms by Site
Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Biliary Tract Diseases
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes

“Some of these orphan drugs have managed to generate significant Medicare expenditures and billions of dollars in annual revenue while treating only rare diseases and conditions.“

ORPHAN PRODUCT GRANTS PROGRAM
Under the FDA’s Orphan Products Grants Program, clinical investigators may be awarded grants to support the development of safe and effective medical products for patients with rare diseases. The program has supported clinical trial research since 1983 and has funded successful rare disease clinical trials that have facilitated the approval of more than 80 products.

MEDICARE COVERAGE
Orphan drugs are generally covered by Medicare, which helps ensure that patients have access to these treatments. Most of the highest-expenditure drugs in Medicare have been granted at least one orphan designation, qualifying their manufacturers for Orphan Drug Act financial incentives. According to the US Department of Health and Human Services Office of Inspector General:
“Some of these orphan drugs have managed to generate significant Medicare expenditures and billions of dollars in annual revenue while treating only rare diseases and conditions. However, orphan drugs are not limited to the treatment of rare diseases or conditions. Although the vast majority of orphan drugs treat only rare diseases or conditions, many of the high-expenditure orphan drugs included in our review were originally approved—and are still primarily used—to treat relatively common diseases or conditions.”
Furthermore, orphan drug exclusion from specific pricing plans could provide significant financial incentives for drug manufacturers to seek orphan designation for drugs approved to treat common diseases or conditions.

https://within3.com/blog/orphan-drug-incentives-guidelines

Grants, research design support, FDA fee waivers, tax incentives, and orphan drug market exclusivity are the main incentives for orphan drug R&D. Although the 7-year orphan drug market exclusivity provision had a positive yet relatively modest overall effect on effective patent and market exclusivity life, economic incentives and public support mechanisms provide a platform for continued orphan drug development for a highly specialized market.

In 1983, the ODA charged the FDA with the role of reviewing and approving requests for orphan product designation, overseeing the seven year exclusive marketing for orphan products, coordinating research study design assistance for sponsors of orphan drugs, encouraging sponsors to conduct open protocols, and awarding grants for development of orphan drugs.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631478/

Timster
I think Avacta qualify,

The grants are available to any foreign or domestic, public or private, for-profit or nonprofit entity (including state and local units of government). Federal agencies may not apply.

The purpose of this RFA is to fund clinical trials in support of a new indication or change in labeling of products to address unmet needs in rare diseases or conditions. The study protocol proposed in the grant application (including studies of already approved products evaluating new orphan indications) must comply with the applicable regulations in 21 CFR 312 for drugs and biologics and 21 CFR 812 for devices, with the exception noted above. An active (e.g., non-exempt and non-hold) IND/IDE is required, except for medical foods that do not need premarket approval and medical devices that are classified as non-significant risk (NSR). Applicants studying an NSR device need to provide a letter in the grant application from FDA's Center for Devices and Radiological Health indicating the device is an NSR device.
The final version of the protocol that is submitted with the grant application must be the protocol that was submitted to the applicable FDA IND/IDE review division. This protocol should have been submitted to the FDA review divisions a minimum of 30 days before the grant application deadline. Be sure to indicate in the IND cover letter to the review division your intent of applying for an FDA Office of Orphan Products Development Clinical Trials grant and how the study will be used for future marketing approval and product development. This will allow the review division to assess the IND. To qualify for programmatic/scientific review, the study protocol proposed in the grant application must be deemed as safe to proceed under an active IND or IDE (i.e., not on clinical hold and not exempt).

Another shock for the
Fud Team.

Only UK trials need funding unless UK Gov give grants.

USA trials for ODD receive grants of $650k per year.

Only clinical trials of products evaluating efficacy and/or safety in support of a new indication or change in labeling of products to address unmet needs in rare diseases or conditions will qualify. 

Another box ticked…..

ODD grants in the USA
Application budgets are limited to $650,000 per year in total costs (direct and indirect costs) for up to a maximum of four years of support. Detailed budgets for each requested year need to reflect the actual needs of the proposed project including both direct and indirect costs. 

https://www.fda.gov/industry/faqs-orphan-products-grant-applicants

FDA approval for Avacta will happen much quicker.

Watch this video it’s very interesting you would think they could be talking about AVA6000 and a 50 year old drug called doxorubicin.
Avacta have timed this trial perfect for these new changes from FDA and NCI

https://www.urotoday.com/video-lectures/asco-gu-2023/video/3244-new-nci-fda-unit-aims-to-streamline-drug-development-for-cancer-patients-michael-morris.html

I think that across the drug development spectrum between agencies and the government, there is recognition that there is a role for having a really accelerated method of getting drugs to patients who need it and who will most benefit by it as quickly as possible, in which you would say it's not business as usual, and we're going to create this mechanism so that patients get access to the drugs they need as fast as they can.

Pre/Cision born in the USA in a Tuffs university Lab.

It will come of age in the USA when it gets FDA accelerated approval in the near future.

Then probably bought and brought back to the USA by a Big American Pharma Company.

GLA keep hold of those golden tickets…

It works

AVA6000 is very similar to a standard chemotherapy drug called doxorubicin. Like doxorubicin, AVA6000 works to slow or stop the growth of cancer cells by blocking an enzyme.

That’s some cancers to go at:
Diseases
Breast Cancer
Colorectal Cancer › Colon Cancer
Colorectal Cancer › Rectal Cancer
Genitourinary Cancer › Bladder Cancer
Gynecologic Cancer › Ovarian Cancer
Head & Neck Cancer
Hepatobiliary
Hepatobiliary › Pancreatic Cancer
Lung Cancer › Lung Cancer, Non-Small Cell
Prostate Cancer › Metastatic Disease after Hormone-Reducing Therapy
Sarcomas
Solid Tumors
Upper Gastrointestinal › Esophageal Cancer
Upper Gastrointestinal › Pancreatic Cancer

Here we go USA
Game on go go Avacta

https://www.mskcc.org/cancer-care/clinical-trials/22-428

Wholly owned

“ Avacta's Therapeutics Division, a clinical stage oncology drug innovator, is building a wholly owned pipeline of novel Affimer® immunotherapies and pre|CISION™ tumour targeted chemotherapies.”

Lots of change coming from the FDA.
I think Avacta have a really good chance of Accelerated Approval.

Q: What is Project Optimus? 
A: Project Optimus is an initiative to shift the dose optimization and dose selection paradigm away from ”maximum tolerated dose” in oncology drug development. This is a relatively new initiative; we are working with sponsors to integrate this into earlier stages of development. 

Click on Supplemental FAQS

https://www.fda.gov/about-fda/oncology-center-excellence/project-socrates