Replies to post #527 on Biotech Ideas

[gfp927z]

Blade, Looks like the armed MAB technologies have progressed a lot since the IMGN days :o)


Mersana - >>> DolaLock Technology

https://www.mersana.com/our-technology-platforms/dolalock-technology/

Once ADCs release their cytotoxic payload into targeted cells, the drug is often able to cross cell membranes, entering and potentially killing neighboring cells whether those cells are cancerous or not. This effect is called bystander-killing, which is advantageous when bystander cells are cancerous but toxic if the cytotoxic drug is able to enter adjacent healthy cells.

The DolaLock payload controls the bystander effect by locking the cytotoxic drug inside cells after allowing a short period of diffusion throughout the tumor. As the drug diffuses through neighboring tissue, the DolaLock payload is metabolized to a form that is still highly potent but no longer able to cross the cell membrane. DolaLock effectively locks the drug inside cells, controlling the bystander effect for a safer and more effective cancer therapy.

Our DolaLock payload is a proprietary auristatin cytotoxic drug and is a highly potent anti-tubulin agent selectively toxic to rapidly dividing cells.

A common mechanism of resistance in cancer is the up-regulation of multi-drug resistance (MDR) pumps, such as PgPs, which actively pump drugs out of cancer cells to help them survive. Our DolaLock payload cannot be pumped out by PgPs, thereby avoiding this resistance mechanism. In addition, our proprietary auristatin payload has also been shown in preclinical tests to cause immunogenic cell death and to stimulate the immune system through dendritic cell activation. Because of this, synergy with immuno-oncology agents such as PD-1 inhibitors has been observed in preclinical models. Our DolaLock payload with controlled bystander effect allows us to create ADCs that produce a highly potent, well-tolerated, and specifically-targeted cancer therapy.<<<



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[bladerunner1717]

MRSN initiated at Citi with a $12 price target.


With Upcoming Ovarian Cancer Data, Analyst Sees 100% Upside For Mersana Therapeutics
Vandana Singh
Fri, January 20, 2023 at 12:16 PM PST
In this article:

MRSN
+9.97%


Citi initiated coverage on Mersana Therapeutics Inc (NASDAQ: MRSN) with a Buy rating and a price target of $12.

The analyst says the topline registrational data (expected in mid-2023) from the UPLIFT Ph2 study evaluating upifitamab rilsodotin (UpRi; NaPi2b ADC) in platinum-resistant ovarian cancer (PROC) will be a catalyst of significant debate.

Citi analyst says that while readout will be binary, investors are underappreciating UPLIFT’s probability of success in NaPi2b-high patients, given the promising efficacy observed in Phase 1.

If the UPLIFT study results are positive, it will lead to a clear pathway to an accelerated approval filing by YE23.

The analyst writes that UpRi’s durability in Phase 1 was in-line or better than single-agent chemo SOC and the recently approved ADC Elahere.

On toxicity, reduced dosing and patient selection strategies should mitigate the risk of Gr4/5 pneumonitis seen earlier in Phase 1.

In December, Mersana announced its third significant collaboration agreement in 2022, reflecting its increasing role as an ADC partner.

The company announced a research collaboration and commercial license agreement with a subsidiary of Merck KGaA (OTC: MKKGY) to discover novel Immunosynthen ADCs directed against up to two targets.

Mersana received an upfront payment of $30 million and is eligible to receive reimbursement of certain costs, up to $800 million in potential milestone payments.

Price Action: MRSN shares are up 10.48% at $6.43 on the last check Friday. (Up more in AH.)

Bladerunner