Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Immunotherapy

Posts tagged ‘Antibody Drug Conjugate’

Red and green flags for CytomX’s CX-2051 in CRC

Yesterday heralded an unexpected surprise in the antibody-drug conjugate (ADC) niche with CytomX’s announcement regarding the initial phase 1 data on their molecule (CX-2051), an EpCAM-targeting agent.

It has emerged as a potential competitor in late line metastatic colorectal cancer (CRC), a disease where new treatments are needed.

Early data in a small sample of cancer patients, however, are notoriously difficult to predict in terms of future outcomes.

EpCAM-based antibodies are not new since several have already come and gone off to dog drug heaven already. So what’s unique about this latest agent and will it the change the pattern of negative outcomes we’ve seen so far? After all, this might indicate some essential differences, yet they may not necessarily translate to more success from a clinical perspective.

In our latest analysis we explore a number of factors, which could help us get a grip on just where this might be headed…

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Thinking outside the box

I’ve heard quite a few people frequently exclaim of late how “ADCs are hot!” Alrighty then, yet this is really only the end of the beginning because old hands know they have actually been around for quite a while.

If one was cynically minded then there’s an obvious reason – chemotherapies are usually generic these days, while ADCs bring in much higher ticket prices.

They won’t all succeed though – we’ve already seen a steadily growing graveyard of failures, which started out promising on paper then unfortunately flopped in the clinic.  Just because an area is suddenly declared hot (again) doesn’t guarantee success because these are complex molecules to design compared to small molecules with a lot of factors impinging on their performance.

What many observers have missed, however, is the deeper and broader opportunities offered beyond the often plain vanilla examples.

This is because the modality has greater flexibility than chemotherapies – you can design them such that other things can be bolted on or even hidden, Trojan horse style.

In other words, what we are seeing is an early trend with few enlightened companies starting to ‘think outside the box’ in this niche.

In the near to medium future we will see a greater volume of clinical data on these emerging approaches, which could lead to improved outcomes and longer lives for people living with cancer.

So what are these new fangled things, how do they work, and which companies are active in the futuristic ADC markets?

In this review we highlight half a dozen emerging areas around ADC technology with examples of products and companies active in these niches…

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ESMO Preview 2 – Making sense of controversy

Plaza de Cibeles, Madrid

In our latest ESMO preview series, we selected a modality to focus on and explore the potential opportunities and challenges many will face in the clinic.

There are a number of issues to address in this space:

  • Will new developments in technical design features help us see more agents over the finish line or are they doomed to repeat the mistakes of past?
  • As we see a much broader range of targets being evaluated, will this help or hinder the process?
  • What factors need to see improvement if we want to increase the number of Health Authority approvals?

There is no doubt the face of oncology R&D is changing – will recent successes help others over the line as well?  To find out, we looked a large number of abstracts and selected some for discussion.

Here are our insights on the current state of play…

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The dog that didn’t bark

What do cancer drug development and Sherlock Holmes have in common?

The simple answer is that sometimes you can gain insights by looking at what did not happen.

Will belantamab mafadotin stand out in the crowded BCMA space?

In 1892 Sir Arthur Conan Doyle wrote a short story about the disappearance of a famous racehorse the night before a race. What was curious about the incident was that there was no barking from the watchdog when you might otherwise have expected it, suggesting the dog knew the thief…

Can we follow the same inductive reasoning when it comes to cancer drug development? Are there things we would expect to see, but don’t? If so, what inferences can we draw from them?

In this post we’re taking a closer look at the latest data for GSK2857916 (now belantamab mafadotin), which in many ways was “the dog that didn’t bark” at ASH19.

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Seattle Genetics vadastuximab talirine and liver toxicities in AML

Yesterday sudden and unexpected news from Seattle Genetics caused quite a stir…

“Seattle Genetics Announces Clinical Hold on Several Phase 1 Trials of Vadastuximab Talirine (SGN-CD33A).”

Part of the Seattle Genetics exhibit booth at #ASH16, taken with permission

In short, over 300 patients have been treated with the ADC and six experienced hepatotoxicity, including several cases of veno-occlusive disease, with four fatalities.

We’ve written about AML several times recently and also received a number of reader questions on this latest development, so it’s time to explore the issue in more depth and look at the implications. We also include some expert commentary from a leukemia specialist for their take on the issue.

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ASCO 2014 Diffuse Large B Cell Lymphoma DLBCL Progress

One of the overlooked highlights from ASCO this year was new data in diffuse large B cell lymphoma (DLBCL), which is an aggressive form of Non-Hodgkins Lymphoma (NHL). DLBCL is the most common form of NHL accounting for nearly one third of newly diagnosed NHL cases each year in the USA. Most of these people are adults rather than children.

The first sign of DLBCL is often a painless rapid swelling in the neck, armpit, or groin, which is caused by enlarged lymph nodes. Other symptoms can include night sweats, unexplained fevers, and weight loss.

Aggressive lymphomas such as DLBCL behave very differently from indolent NHL (iNHL) since they are faster growing and generally have a much poorer prognosis. As a result, they are treated much more aggressively with rituximab plus chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Sometimes etoposide (E) is added in younger patients with a high disease burden, in which case the regimen is known as R-EPOCH.

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AACR 2013 DMUC5754A is a novel agent for Ovarian Cancer

The cherry blossoms are finally blooming in Washington DC for the 2013 annual meeting of the American Association for Cancer Research (AACR).

With AACR in DC this year, the following traditional Japanese haiku published on the National Park Service website struck me as appropriate for cancer researchers and survivors to reflect on:

Yo no naka wa, Mikka minu ma ni, Sakura kana

“Life is short, like the three day glory of the cherry blossoms.”

Yesterday at AACR was predominantly an educational day, but several studies were highlighted to the assembled media.  One of the late-breaking clinical trials that caught my attention was the preliminary phase 1 data on Genentech’s novel new agent DMUC5754A.

LB-290 Targeting MUC16 with the Antibody-Drug Conjugate DMUC5754A in patients with platinum-resistant ovarian cancer.  This data will be presented by Joyce Liu, MD, MPH from Dana-Farber Cancer Institute in the Clinical Trials Symposium on Tuesday, Apr 9 at 4.00 pm.

Dana-Farber issued a press release yesterday  – here’s the link. The picture of Dr Liu is from her Dana-Farber profile.

Ovarian cancer causes more deaths in women than any other cancer of the reproductive organs, with an estimated 20,000 women diagnosed with this cancer each year.  The majority of women are treated with traditional platinum based chemotherapies, and most of these relapse and develop drug-resistant disease.  This makes the development a new novel agent such as DMUC5754A that will treat platinum-resistant ovarian cancer a major potential breakthrough.

In an AACR media release, Dr Liu commented on how the drug works:

“This drug consists of an antibody and a potent toxin joined by a cleavable linker. The antibody identifies a protein, MUC16, which is highly expressed in ovarian cancers, and targets the toxin to kill the cancer cells.”

Liu went on to note that, “Unlike other cancer treatments, the antibody-drug conjugate releases the toxin with relative selectivity to the MUC16-positive cancer cells.  This allows delivery of drugs that would otherwise be too toxic for treatment.”

According to Liu, “If the activity of this drug is confirmed in additional trials, this will represent a novel type of therapy for ovarian cancer, with effectiveness in platinum-resistant ovarian cancer, which is the hardest type of ovarian cancer to treat.”

Genentech are particularly good at sharing early data at AACR, and based on the promising responses in MUC16 IHC 2/3+ patients, this new ADC compound is likely to progress to phase 2 – a compound to watch out for in the future.

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