Lacerta Bio is a business development consultancy specializing in identifying, assessing, negotiating, and closing licensing and partnership opportunities for the pharmaceutical, biotechnology, and drug delivery industries.
We also work with and support internal business development teams with market research, competitive intelligence, financial modeling, and other support services.
If you need assistance finding or assessing business development and/or partnership opportunities, contact us at email@example.com.
Background GPR119 Activation leads to glucose-dependent insulin secretion and the release of GIP and GLP-1. This mechanism has generated a great deal of excitement in the diabetes research community, as it strongly mimics processes which take place during digestion. Additionally, this mechanism is superior to GLP-1 only approaches, without the problems associated with sulfonylureas andRead More»
Anaplastic Lymphoma Kinase (ALK) is emerging as an important target for novel, safe, oral anti-cancer therapies. First identified in 1994, ALK is believed to affect nearly 100,000 new NSCLC patients globally. In fact, ALK inhibition has potential in a wide variety of cancers, such as NSCLC, Lymphomas, inflammatory myofibroblastic tumors (IMT), neuroblastoma, and ovarian cancers. Our client’sRead More»
Background There are two general mechanisms of action for treating osteoporosis: Anti-Resorption Agents inhibit the normal resorption of bone, thereby slowing bone loss. But, this approach does not trigger de novo bone formation. Biphosphonates like zoledronic acid and disodium pamidronate are marketed examples of anti-resorption agents. Anabolic Agents are a relatively new approach to treatingRead More»
At Lacerta Bio, we’re big believers in the therapeutic benefits of drug delivery in its many forms.
Today, another drug delivery effort earned an FDA approval. In this case, it’s naloxegol from Nektar (and its partner, AstraZeneca). Naloxegol was approved for the treatment of opioid-induced constipation.
Naloxegol is a highly interesting molecule because it consists of a molecule of naloxol to which a 7-mer liner PEG is attached.
Now the PEGylation of peptides and proteins is a well-established method for conferring extended half-lives and preferential uptake properties to these molecules.
So why PEGylate small molecules?
There are a few reasons:
Increase aqueous solubility – Short Strands of PEG are highly water-soluble, and they can “pull” less soluble drugs into solution, thereby enhancing oral bioavailability.
Decreased toxicity – PEGylated small molecules are generally cleared hepatically. So reducing renal clearance (and hence renal toxicity) can be addressed via PEGylation. Add enough PEG, and oral absorption could be dramatically reduced, if that is what is desired.
Interestingly, the PEGylation of small molecules is not restricted to parenteral drugs. Oral drugs, such as acyclovir, may provide incremental clinical and safety benefits through PEGylation.
A terrific review article from 2013 (large PDF file) discusses the 20-25 PEGylated small molecules which are in various stages of development (of which four were in the clinic at the time of publication).
A few of them stand out as interesting in our mind:
PEG-ironotecan (NKTR-102) – Nektar has developed a PEGylated version of the cancer drug ironotecan. It is currently in a variety of clinical studies for metastatic breast and other cancer indications. The increase in molecular weight due to PEGylation results in a 300-fold increase in preclinical efficacy compared with native drug. Clinically, drug half life is extended to the point where dosing can be performed on a weekly schedule, and with a much higher maximum tolerated dose.
PEG-SN38 (EZN-2208) – SN38 is a camptothecin with poor water solubility. In fact, it is so poor that intravenous administration is not feasible. Enzon developed a PEGylated version, and reported promising Phase II results in metastatic breast cancer.
PEG-docetaxel (NKTR-105) – Docetaxel is a highly effective antineoplastic agent. However, clinical use is limited due to side effects. A PEGylated version similar to PEG-ironotecan was prepared, and demonstrated superior Preclinical performance compared to native drug. It appears that Nektar has since dropped this program.
The notion of solving PK or other problems with PEGylation has been extended beyond the cancer drugs. Antivirals (such as PEG-acyclovir), antifungals (PEG-amphotericin B), and immunosuppressants (PEG-tacrolimus) are all small molecules which may benefit from PEGylation.
An interesting idea is to use PEGylation to reduce CNS exposure to drugs such as opioids and anti-histamines. Thus, a PEGylated form of diphenhydramine could be a highly effective anti-histamine without the sedation associated with the native drug.
What is really exciting about this approach is that the PEGylation chemistries have become far more sophisticated. As a result, very precise chemistries can be used to generate PEGylated small molecules that are much easier to synthesis and purify.
Currently, Nektar is at the forefront of this approach. But it is likely that several academic researchers and companies (such as BiogenIdec) will continue to explore this approach to solving problems associated with established small molecules.
This morning, California-based Avanir Pharmaceuticals announced that their combination of dextromethorphan HBr and quinidine sulfate (AVP-923) hit their Phase II endpoints in Alzheimer’s Disease: Treatment with AVP-923 was associated with significantly reduced agitation as measured by the primary endpoint, the agitation/aggression domain score of the neuropsychiatric inventory (NPI) compared to placebo (p=0.00008). The reduction
Thompson Reuters published a good overview of the challenges facing companies developing biosimilars. A few items which stood out for us were: Europe Has Led, But… – While 17 biosimilars have been launched in Europe, the path has been slow and uncertain. Pricing for biosimilars remains high, and issues such as product naming and
A few weeks ago, BIO conducted an interesting panel discussion as part of their run up to the BIO Latin America Conference taking place the week in Brazil. The panel included business development professionals from a wide range of companies in Latin America, primarily Brazil. Here are a few comments and issues which stood