ARX517-2011

[NewGame]

Has anyone participated in this trial at Weill Cornell in NYC? If so, what has been your experience? Thank you.

[MelodyCat]

I am not in the trial but it does look interesting. There hasn’t been much success with monoclonal antibodies with PCa because of a lack of Tcell receptors. This approach is different in that it is used as a carrier to inject a cytotoxic substances on a selective (PSMA expressing) basis. The company, AMBRX Pharma was recently bought by Johnson & Johnson for $2billion. This indicates there is something to the story to back up early clinical results. BTW, I was in the finance industry all my life so I saw the good and bad. In the past, many of us believe this would be done to bury new therapies to protect the profits for older less-effective therapies. Could be this time too but maybe the cat is out of the bag finally. Not to be political but the new administration has a tendency to pull masks off and may not let good solutions be buried. Time will tell on that one.

[Seasid in reply to MelodyCat]

DeepSeek said

The discussion revolves around a novel approach to treating prostate cancer (PCa) using antibody-drug conjugates (ADCs) developed by AMBRX Pharma, recently acquired by Johnson & Johnson (J&J) for $2 billion. Here's a structured analysis of the key points:

### **1. Scientific Innovation: ADCs vs. Traditional mAbs**

- **Monoclonal Antibodies (mAbs) Limitations**: Previous mAbs in PCa faced challenges due to poor T-cell engagement, as many therapies rely on immune activation (e.g., checkpoint inhibitors). PCa’s "cold" tumor microenvironment (low immune infiltration) limits efficacy.

- **AMBRX’s ADC Approach**: Their ADC (ARX517) targets prostate-specific membrane antigen (PSMA), a validated biomarker in PCa. ADCs deliver cytotoxic payloads directly to cancer cells, bypassing the need for T-cell activation. This site-specific delivery minimizes systemic toxicity and enhances precision compared to traditional mAbs.

### **2. PSMA Targeting Validation**

- PSMA is highly expressed in metastatic castration-resistant PCa (mCRPC). Existing PSMA-targeted therapies (e.g., Pluvicto, a radiopharmaceutical) demonstrate clinical success, validating the target. AMBRX’s ADC could complement or compete with these therapies, offering a different mechanism (chemotherapy vs. radiation).

### **3. J&J’s Acquisition & Strategic Implications**

- **Platform Potential**: AMBRX’s proprietary ADC technology uses site-specific conjugation (using non-natural amino acids), improving stability and efficacy over older stochastic conjugation methods. This platform may have broader applications beyond PCa.

- **J&J’s Oncology Portfolio**: J&J has a strong interest in PCa (e.g., apalutamide, abiraterone). Acquiring ARX517 aligns with their strategy to dominate the PCa market, especially if early-phase trials show promising efficacy/safety.

### **4. Clinical Context & Challenges**

- **ARX517 Status**: Phase 1/2 trials (APEX-01) are ongoing. Key questions include:

- **Toxicity**: Can the ADC avoid off-target effects common with payloads like microtubule inhibitors?

- **Heterogeneity**: Will PSMA-negative tumor cells drive resistance?

- **Competition**: How will it differentiate from Pluvicto or other ADCs in development (e.g., Astellas/Pfizer’s enfortumab vedotin for other cancers)?

### **5. Industry Practices & Political Influence**

- **"Burying Therapies" Narrative**: While strategic portfolio decisions occur, outright suppression of effective therapies is unlikely in a transparent regulatory environment. Large acquisitions like J&J/AMBRX typically aim to accelerate development, not stifle it.

- **Regulatory Landscape**: A new administration could impact funding or FDA priorities (e.g., faster approvals, expanded access), but FDA decisions remain data-driven. Political shifts may affect funding for oncology research or drug pricing policies.

### **6. Risks & Uncertainties**

- **Clinical Data**: Early results (e.g., response rates, safety) will determine ARX517’s future. ADCs historically face challenges with payload toxicity and manufacturing complexity.

- **Market Dynamics**: J&J’s investment doesn’t guarantee success, but reflects confidence in the platform. Competition with radiopharmaceuticals and other ADCs will require clear differentiation.

### **Conclusion**

AMBRX’s ADC represents a promising, mechanistically distinct approach to PCa, validated by J&J’s acquisition and the broader success of PSMA-targeted therapies. While historical skepticism about pharmaceutical practices is understandable, the acquisition suggests J&J intends to advance this therapy. Clinical data, regulatory decisions, and competitive dynamics will ultimately determine its impact. The political environment may influence funding and approval timelines, but efficacy and safety remain the primary hurdles.

DeepSeek said

[MelodyCat in reply to Seasid]

I have seen more use of AI here than anywhere else but maybe I live a sheltered life. Can’t say there were any inaccuracies. My concern, like many is that it is a great aggregator of what is known but isn’t really intelligence which is more intuitive, explorative and imaginative. I care because any good tool can be improperly used like calculators…just watch a cashier try to make change on their own. Breakthroughs come from taking chances and the creative ability of the mind. At least it is more useful than ChatGPT!

[Seasid in reply to MelodyCat]

I am using ChatGPT even for advice how to make coffee with the plunger etc. I believe we in Australia are using AI so much that our government is concerned that all the information will end up in a wrong hand.

I don't really care for that.

[MelodyCat in reply to Seasid]

Greeting to the downunder. My best friend just got back from a visit and loved the land and people! Lots of similar discussions up here in the States. In my opinion, it is just about impossible to stop the flow of information both good and bad. As for Chat, I was more focused on how our college students aren’t writing their own stuff. Maybe Chat will be the new YouTube DIY videos..

[pakb in reply to MelodyCat]

This administration has cut funding to cancer research. Interpret that as you wish- but I know several in my cancer groups who have had their clinical trials canceled due to recent (last few weeks) funding fears and executive orders. My daughter's best friend is a biology doctoral student at University of Pennsylvania, PENN, and their research has been halted. No one is burying solutions that pass scientific efficacy and safety regulations. In my opinion, I'm glad that 'solutions' are subject to rigorous testing and research prior to being released.

[MelodyCat in reply to pakb]

Just a couple of follow up questions none of which should be construed as support for ANY government administration as I worked in government for my last 15 years so I have some idea of the good and bad. Why would clinical trials be immediately cancelled due to a “fear” of funding issues? Isn’t the funding procured first or at least wait until you are more certain there is a financial issue? I am also curious why an institution like UPENN has to cancel everything when they have a $22 billion endowment - it is a valid question. You are also, with all due respect, not able to affirm that “no one” is letting financial implications drive health care. I have followed medical research for decades and find promising, but not profitable/patentable research ends with “and more research needs to be done” but never happens. It is 2025 and the survival rates for many cancers have not improved much at all but rather speak of breakthroughs for 4 months of OS. At the same time, we have the best iPhones, bombs, AI etc. Sorry about the rant but it is high time we (us fighting the beast) demand results. If you know of a specific EO that directly reduces cancer research, please provide the reference and I will personally draft a letter to RFK Jr. expressing our deep concerns. Finally, I do agree that rigorous testing is necessary before unleashing compounds to the world but there should also be a more accessible option for those whose SOC options are no longer working.

[pakb in reply to MelodyCat]

I was responding to your statement, "In the past, many of us believe this would be done to bury new therapies to protect the profits for older less-effective therapies. Could be this time too but maybe the cat is out of the bag finally. Not to be political but the new administration has a tendency to pull masks off and may not let good solutions be buried. Time will tell on that one." What makes you believe that this is happening? With all due respect, I'm not a fan of putting statements like that out there. That is a conspiracy theory. Our current president absolutely froze monies that go to cancer research. I have people I know personally that had their clinical trials halted. And my daughter's friend at UPenn was told to halt the research they were doing because funding was pulled. And you clearly have a side. Which is fine. I'm stating facts from people I know personally. And I do not put much faith in RFK being receptive to concerns. It's a slippery slope letting people use treatments that haven't gone through necessary testing. I agree that there are those that would love to be in a trial when SOC stops working. That should be opened up and clinical trials should be more accessible. All of that takes money. One of my dear friends is a pediatric oncologist. His wife has stage 3 cancer. He'd like nothing more than to find a cure. It's ridiculous to suggest that solutions are out there that are being suppressed on purpose. Survival rates for many cancers has improved.

[MelodyCat in reply to pakb]

Okay.

[j-o-h-n]

Note this Trial is also being given at MSKcc in NYC.

AI Overview

Learn more

The "ARX517-2011" trial at Memorial Sloan Kettering Cancer Center is a Phase 1 clinical trial investigating the safety, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of a drug called ARX517, likely being tested in patients with metastatic prostate cancer, either alone or combined with androgen receptor pathway inhibitors (ARPIs); this is considered a "first-in-human" study, meaning it is the first time this drug is being tested in humans.

Key points about the ARX517-2011 trial:

Focus on prostate cancer:

This trial is primarily designed to study the efficacy of ARX517 in patients with advanced prostate cancer.

Phase 1 study:

As a Phase 1 trial, the main goal is to assess the safety profile of the drug, including potential side effects, while also exploring its preliminary effectiveness against the cancer.

Dose escalation and expansion:

The study likely involves a dose-escalation phase to determine the appropriate dosage, followed by a dose-expansion phase to further evaluate the drug's activity in a larger patient group.

Combination therapy potential:

The trial may also explore the potential of combining ARX517 with other standard treatments for prostate cancer, like ARPI drugs.

Good Luck, Good Health and Good Humor.

j-o-h-n

[kainasar in reply to j-o-h-n]

Thanks John! Is their a free lunch?

[j-o-h-n]

To kainasar,

Remember what your dear dad told you when you were young "Son, there's no such thing as a free lunch".....

Good Luck, Good Health and Good Humor.

j-o-h-n

[God_Loves_Me]

Yes I did ARX517 5 dosage last year.

Feedback

- It is ADC that combine chemo + immunotherapy

- Side effect include Fatigue, lower platelets

- ARX517 do not have any toxicity so you can take as much as you can.

- ARX517 reduce PSA and also target everything that show up on PSMA.

I had sever kidney damage from the ARX517. I think all patients are monitoring Protein in URINE now.

Advice : Please work with kidney doctor and monitors kidney

[NewGame in reply to God_Loves_Me]

Thanks for the info - so so sorry about the kidney issues. Hope things are better now.

[God_Loves_Me in reply to NewGame]

Now I am ready for next treatment