Member Info for BuenaVista

Oh wow! A whole 9 days to dream up questions about the data that will be presented on the 17th. Thinking cap on!

Christina loves a Thursday RNS, explainer early the following week, share price to dip to 70.

McPumpy

Neighbours Autolus Therapeutics (NASDAQ: AUTL) has never made a profit.

It's all here:

https://www.google.com/search?q=How+are+allogeneic+CAR-T+cell+therapies+for+leukemia+progressing+through+the+regulatory+system%3F

https://www.google.com/search?q=What+are+the+clinical+issues+with+the+allogeneic+CAR-T+cell+therapies+for+leukemia+that+are+in+trials%3F

Some clarification on autologous, allogeneic, ex vivo and in vivo CAR-T cell therapies. These terms describe two fundamental aspects of CAR-T cell therapies: the source of the T cells used for treatment and the location where the genetic modification occurs.

• Autologous (Self-Derived): Autologous therapies use a patient's own T cells as the starting material. This personalized approach ensures the modified cells are a perfect match for the patient's immune system, which eliminates the risk of immune rejection or graft-versus-host disease (GvHD). The main drawbacks are the high cost, complex logistics, and a prolonged manufacturing time of several weeks (the "vein-to-vein" time).

• Allogeneic (Donor-Derived): Allogeneic therapies use T cells harvested from healthy donors to create "off-the-shelf" products that can be mass-produced, stored, and administered immediately when a patient needs treatment. This approach addresses the accessibility and timing issues of autologous therapy, which is crucial for patients with rapidly progressing cancers. However, it requires additional genetic engineering (e.g., using CRISPR) or immunosuppressive drugs to prevent the recipient's immune system from rejecting the donor cells or the donor cells from attacking the patient's body (GvHD).

• Ex Vivo (Outside the Body): This approach involves removing a patient's or donor's T cells from the body (via a procedure like leukapheresis) and sending them to a specialized laboratory. In the lab, the cells are genetically engineered with the Chimeric Antigen Receptor (CAR) construct, multiplied to therapeutic quantities, and then infused back into the patient. This is the manufacturing method used for nearly all currently approved commercial CAR-T cell therapies.

• In Vivo (Inside the Body): This is an emerging, experimental strategy designed to simplify the manufacturing process and reduce costs. Instead of removing cells, the genetic material needed to create the CAR (typically packaged in a viral vector or lipid nanoparticle) is injected directly into the patient's bloodstream. The goal is to program the T cells to express the CAR in situ (within the body itself).

In essence, ex vivo vs. in vivo is about where the engineering happens (outside or inside you), while allogeneic vs. autologous is about whose cells are used (donor vs. patient). HG-CT-1 is an autologous ex vivo treatment.

- - - - -

Allogene is one company pursuing allogeneic CAR-T cell therapy: https://allogene.com/science/

Their ALLO-819 for AML was dropped some time in the last year: https://web.archive.org/web/20241108075452/https://allogene.com/web/20241108075452/https://allogene.com/pipeline/ vs. https://allogene.com/pipeline/

Factors to consider for a winning investment:

• Tech - works, proven, better than current SoC, IP-protected

• Market - Market size, unmet/unrealised need

• Competitive situation - existent tech (esp. from major players), same/similar tech, other new/disruptive tech

• Management - competent, savvy, connected

• Timing - secure future based on...

— Funding - the difficult one - long cash runway, good funding/dilution trade-off options

— External factors - market sentiment, sector sentiment, government actions, market disruptions

You are a manipulative trader Aldebaran, previously appearing as Moneysponge on the AFC and Avacta bbs, inter alia, ramping like Avacta's no1 pom-pom girl until you sold up and disappeared on 13 December 2023.

I've got very little time for you and won't be distracted by what you, yet again, want to talk about. If others bite and take this down the funding route then I will just start a new thread.

On the meantime, maybe you'd like to expand on the "advances being made in in-vivo CAR-T" that you mentioned. Your source for that assertion or some examples would be appreciated.

I've been 'questioning' Haywain to try to get my head around the science and I appreciate his explanations, as I am also grateful for JHFH's contribution on the history of the company.

Thinking for myself? Everyone should. Facts are more important than opinions when there are promoters and detractors out to influence opinion, particularly when one's own money is involved.

There's more to a winning investment than just good tech. I'll expand on that when I'm on my laptop.

You don't ask, you don't learn. I'd rather know what I'm getting into than be one of the munchkins here.

Well at 5:50 she talks about ESMO 'last week ' in Berlin.

Those do look like decorative lights being the double door. Maybe for Hallowe'en?

Good summary. Thanks for the explanation.

Comment?

😂 Caught out by the 'less than'.

'LYT-200 demonstrated favorable tolerability and strong efficacy in a heavily pretreated population, both in combination with standard of care and as a monotherapy, supporting advancement toward a potentially registrational Phase 2 trial

'Initial median overall survival of 13.2 months observed in the combination cohort at the proposed Phase 2 dose, exceeding expected late-line relapsed/refractory setting survival of <2.5 months; overall survival data at this dose continue to mature with final results expected in 1H 2026

'Responses observed in patients with high-risk mutations, suggesting potential broad applicability'

"For patients whose AML has progressed, survival is often measured in months, and the toxicities of additional treatments frequently limit what we can realistically offer. What stands out with the LYT-200 data is not only the durable responses we have seen and the ability for some patients to proceed to transplant, but that these outcomes were achieved with a highly favorable tolerability profile," said Amir T. Fathi, MD, Program Director of the Center for Leukemia at the Massachusetts General Hospital Cancer Center and Associate Professor of Medicine at Harvard Medical School. "LYT-200 is not a targeted therapy in the traditional sense; it targets galectin-9, a foundational driver of leukemia biology. The significance of this approach is evidenced by the activity observed across multiple high-risk mutations, suggesting LYT-200 may be uniquely applicable across a broad patient population. Coupled with the emerging overall survival signal at the proposed Phase 2 dose, these data provide strong clinical rationale to advance LYT-200 into late-stage development for the treatment of AML."

'LYT-200 demonstrated favorable tolerability and strong efficacy in a heavily pretreated population, both in combination with standard of care and as a monotherapy, supporting advancement toward a potentially registrational Phase 2 trial

'Initial median overall survival of 13.2 months observed in the combination cohort at the proposed Phase 2 dose, exceeding expected late-line relapsed/refractory setting survival of

OK, thank you, it was not to do with IP issues but what you wrote and the other possibility that had occurred to me - laxer regulatory oversight.

The private company Silver Falcon Ltd was incorporated on 13 February 2013 and subsequently listed on the London Stock Exchange as Silver Falcon Plc on 25 November 2014. It wasn't until 4 October 2017 that, with the reverse takeover, the company became Hemogenyx Pharmaceuticals Plc.

https://find-and-update.company-information.service.gov.uk/company/08401609

AI Overview

Silver Falcon plc chose to list in the UK, and not the US, primarily due to the nature of the company as a special purpose acquisition company (SPAC) or "cash shell" and the more flexible regulatory environment of the London Stock Exchange (LSE) for such listings at the time.

Key reasons for the UK listing included:

• Type of Listing: Silver Falcon secured a standard listing on the Official List of the LSE, which had less stringent regulatory requirements and ongoing obligations compared to a premium listing or a listing on major US exchanges like NASDAQ or the NYSE. The company's prospectus explicitly noted that its shares had not been approved by the US Securities and Exchange Commission (SEC), indicating a deliberate choice to avoid the US regulatory framework.

• Directors' Expertise and Network: The founders and directors, including Geoffrey Dart and Peter Redmond, were UK-based corporate financiers with extensive experience in listing companies, particularly shell companies and those undergoing reverse takeovers, on the LSE and AIM markets.

• Purpose as a Cash Shell: Silver Falcon was established with the specific aim of identifying and acquiring a promising private company (a reverse takeover candidate) to bring to the public market. The LSE, particularly the standard listing segment, was a common venue for this type of investment vehicle in the UK.

• Access to Capital: Listing in London provided access to the UK and European investor base necessary to raise capital for the initial shell operations and the subsequent acquisition of the US-based Hemogenyx Pharmaceuticals LLC.

The US operating subsidiary, Hemogenyx LLC, remained a US entity focused on research, development, and seeking FDA approval for its products, while the parent company (Hemogenyx Pharmaceuticals plc) was headquartered and listed in London.

Latest LYT-200 development here:

Gallop Oncology announces positive initial topline data from Phase 1b trial of LYT-200 in relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndrome. Details to be shared at the 67th American Society of Hematology (ASH) Annual Meeting today, 6th December.

Puretech RNS released at 6pm yesterday: https://www.londonstockexchange.com/news-article/PRTC/prtc-s-gallop-positive-initial-topline-aml-data/17361726

Poster: https://static1.squarespace.com/static/6509f84ba8217f0be44aecd5/t/67bf7eb222b2443bffcc9d15/1740603059491/1499%5B96%5D.pdf

I do find it very strange that this American company is headquartered in the UK and only listed in London. Does anyone know why this is?

It occured to me that, as the basis of this tech was done whilst Vlad was at Cornell and there are two granted US patents for which he is inventor that are assigned to Cornell University...

Reprogramming of human endothelium into hematopoietic multi-lineage progenitors by defined factors ( https://patents.google.com/patent/US10113149B2 ) priority 15/01/2014, granted, expiry 15/01/2034

and

Post-natal hematopoeitic endothelial cells and their isolation and use ( https://patents.google.com/patent/US10570373B2 ) priority 13/11/2014, granted, expiry 14/02/2035

...it may be that he and his wife, who is an IP expert, set up Silver Falcon Ltd, the original precuror to Hemogenyx, in the UK on 13/02/2013 under UK jurisdiction in order to avoid any claim on intellectual property rights by Cornell. Has he ever said why he set up a company in the UK and subsequently listed it (as Silver Falcon Plc) outside the US?

@Knotagain, one could say the interview was too nice but that would be an understatement.

CC said that ESMO had been the previous week so the interview was recorded at the tail end of October, so 5 or 6 weeks ago. Why the delay? Was the release timed to coincide with the Tumour Models Summit? (😂)