Peptide Trends April 2016

April 30, 2016



Bachem‘s pipeline contains more than 200 customer projects in (pre)clinical phases. They all have promising potential: in the last two years, a number of products in phase III trials received marketing authorization and phase II projects progressed to phase III clinical trials. Our services include pegylated peptides, peptides for conjugated NCEs and sterile fill and finish (Clinalfa®).

Our Business Development Executives would be glad to present details of our capabilities. We have the capacity to produce peptide API in quantities of hundreds of kilograms and small molecules in tens of tons per year.

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Diabetes mellitus is a chronic metabolic disorder, characterized by hyperglycemia. The disease can be divided into two main types. Type 1 also known as insulin-dependent diabetes mellitus (IDDM) and type 2 or non-insulin-dependent diabetes mellitus (NIDDM). The absolute lack of insulin, due to destruction of the insulin producing pancreatic β-cells, is the particular disorder in type 1 diabetes.

Type 2 diabetes is mainly characterized by the inability of cells to respond to insulin. The condition affects mostly the cells of muscle and fat tissue, and results in a condition known as „insulin resistance“.

In a normally regulated organism, cells send information to pancreatic β-cells for their need of insulin, in order to uptake glucose. The messenger of this process is still unknown.

In the case of insulin resistance of tissues, β-cells try to maintain normal glucose levels by increasing insulin secretion. If they are not capable to do so, blood glucose concentrations do increase.

There are various approaches with drug therapeutics to reduce blood glucose concentrations.

Gastro-intestinal tract

Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) act on pancreatic islet β-cells. GLP-1enhances insulin secretion by β-cells and also reduces glucagon secretion by α-cells. The effect on suppression of glucagon levels by acting on α-cells is uncertain.

The GLP-1 receptor agonists exenatide, liraglutide, lixisenatide, albiglutide or dulaglutide mimic or improve the effect of GLP-1. There are ongoing efforts to improve pharmacokinetics and –dynamics with these peptides.

New approaches are based on the theory that alterations in gastrointestinal hormones like GLP-1, oxyntomodulin and peptide YY do improve glycemic control. Research groups are working with these peptides and combinations.

Pramlintide slows gastric emptying and glucose absorption. It is approved by the FDA but not by the EMA.

Another possibility to increase GLP-1 levels is by inhibiting dipeptylpeptidase 4 (DPP4), which is responsible for degradation of GLP-1. These gliptins are marketed: sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin.

Inhibition of α-glucosidase slows down the glucose uptake in the gastro-intestinal tract. Marketed inhibitors are acarbose, miglitol and vocarbose.

Bachem offers various products in this research area. Please refer to “Bachem’s contribution to diabetes products” further down.


The biguanide antidiabetic metformin specifically reduces hepatic gluconeogenesis without increasing insulin secretion. It’s mechanism of action is not yet completely clarified. It is recommended as the preferred pharmaceutical agent for type 2 diabetes by the American Diabetes Association.


Improving the responsiveness of pancreatic β-cells to physiological glucose stimuli leads to an increase of insulin secretion. Sulfonylureas and glinides are such insulinotropic antidiabetics. They block K+-ATP-channels, followed by a cascade of opening Ca++ -channels finally leading to increased insulin secretion.


Kidneys are responsible for glucose excretion and reabsorption. Reabsorption is done by sodium-glucose co-transporter 2 (SGLT2). SGLT2 inhibition leads to reduction of blood glucose levels by reducing reabsorption. Marketed products are dapagliflozin, canagliflozin and empagliflozin.


Modified insulins for once daily injection are currently in development. With oral insulins needle sticks could be even avoided and the effect would be more physiological than is with parenteral ones. Several oral insulins are currently in development. Despite drawbacks, also inhaled insulins are still under development.

Bachem’s contribution to diabetes products

Bachem’s portfolio includes commercially available GMP products and a wide range of research grade catalog products.

GLP-1 receptor agonist available as Generic Active Pharmaceutical Ingredients (API):

APIFiling Documentation
Exenatide Acetate*DMF
Liraglutide Acetate*

*All API that are sold for development of drug products still patent protected are offered under Bolar Exemption only. The following disclaimer applies: These products are offered and sold in small quantities only and solely for uses reasonably related to privileged trials and studies for obtaining marketing authorization required by law (Bolar Exemption). Bachem cannot be made liable for any infringement of intellectual property rights. It is the sole and only responsibility of the purchaser or user of these products to comply with the relevant national rules and regulations.

Bachem offers more than 100 Diabetes related research products available online.


Amylins (IAPP) and Fragments (13)

Insulin C-Peptides (10)

Chromogranin A/ Pancreastatin (2)

Exendins and Fragments (13)

Gastric Inhibitory Polypeptide and Fragments (7)

Ghrelin Peptides (4)

Glucagons and Glucagon-Like Peptides (GLP-1 / GLP-2) (27)

Insulin-Like Growth Factors (IGF), Fragments & Related Peptides (10)

Various Products / Diabetes (17)


S. E. Kahn et al., Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future, Lancet 383, 1068–83 (2014)

F. Mittermeyer et al., Addressing Unmet Medical Needs in Type 2 Diabetes: A Narrative Review of Drugs under Development, Current Diabetes Reviews 11, 17-31 (2015)

E. Mutschler, Arzneimittelwirkungen, 10. Auflage, 2013, Wissenschaftliche Verlagsgesellschaft, Stuttgart




Approximately 382 million people worldwide are affected by Type 2 diabetes mellitus (T2DM) (1). T2DM affects many parts of the body and is associated with complications such as heart disease and stroke, blindness, kidney failure and lower-limb damage. In the United States alone, direct medical costs attributed to diabetes were estimated to be $176 billion in 2012 (2). There is a need for new drugs that can more effectively treat T2DM because available drugs are not able to reverse progression of the disease over the long-term.

An estimated 36 peptides are advancing through clinical development for treatment of T2DM as shown in Figure 1 below. Many of these drug candidates are insulins and Glucagon-Like Peptide 1 (GLP-1) receptor agonists. GLP-1 receptor agonists, also known as incretin mimetics, are attractive because they offer glycemic control with a low risk of hypoglycemia. In addition, some GLP-1 receptor agonists have been shown to promote weight loss and reduce systolic blood pressure (3). Several GLP-1 receptor agonists are already approved for the treatment of T2DM including the blockbuster Victoza® (liraglutide), Byetta® (exenatide) and Bydureon® (exenatide), Lyxumia® (lixisenatide), Trulicity® (dulaglutide), and Syncria® (albiglutide) (4).

Figure 1 Number of Peptides in Clinical Development for T2DM (4)



Peptides in Phase III Development

Product NameActive IngredientCompanies InvolvedTarget
Insulin tregopil (IN105)hexyl insulin monoconjugate 2 (pegylated)Nobex Corporation, BioconInsulin Receptor (INSR)
ITCA650exenatideIntarcia Therapeutics IncGlucagon-Like Peptide 1 Receptor (GLP1R)
MK1293insulin glargineMerck & Co Inc, Samsung BioepisInsulin Receptor (INSR)
NN9535semaglutideNovo Nordisk A/SGlucagon-Like Peptide 1 Receptor (GLP1R)
NN9924semaglutideNovo Nordisk A/S, Emisphere, Technologies IncGlucagon-Like Peptide 1 Receptor (GLP1R)
Oral HDV InsulininsulinDiasome Pharmaceuticals IncInsulin Receptor (INSR)
Oral Insulin EXTRAWELLinsulinExtrawell Pharmaceutical Holdings LimitedInsulin Receptor (INSR)
PEX168loxenatide (pegylated)Jiangsu Hengrui, Medicine Co LtdGlucagon-Like Peptide 1 Receptor (GLP1R)
SAR342434insulin lisproSanofiInsulin Receptor (INSR)
SP2086--Jiangsu Hengrui, Medicine Co Ltd, Jiangsu Hansoh Pharmaceutical Co LtdDipeptidyl-Peptidase 4 (DPP4)
UNI-E4exenatide (recombinant)Uni-Bio Science Group LtdGlucagon-Like Peptide 1 Receptor (GLP1R)

Table 1 Peptides in Phase III Development for T2DM (4)


Insulin Receptor Agonists

Biocon is developing insulin tregopil, formerly known as IN105. The product is an oral version of insulin that uses alkyl pegylation technology. Biocon completed a Phase III trial of insulin tregopil in 2011. Subsequently, the company announced that insulin tregopil did not meet the primary endpoint and planned to conduct fresh trials in a re-designed format with a new partner (4). Biocon partnered with Bristol Myers Squibb for the early development of insulin tregopil but the company announced in 2016 that it will conduct the next phase of clinical trials on its own (5).

MK1293 contains recombinant insulin glargine as an active ingredient and is a biosimilar of Sanofi’s Lantus®. Merck & Co Inc (MSD) and Samsung Bioepis are collaborating to develop and commercialize MK1293. In 2015, Merck & Co announced that it completed a Phase III trial to study the safety and efficacy of MK1293 compared to Lantus in patients with T2DM (4).

Diasome Pharmaceuticals Inc is developing Oral HDV Insulin, short acting oral insulin that utilizes Hepatic Directed Vesicles (HDV) insulin technology. Oral HDV Insulin was the first oral insulin approved for Phase III testing by the U.S. Food and Drug Administration. In Phase II studies it has been shown to be effective in lowering blood glucose levels in diabetic patients using low amounts of insulin (4).

SAR342434 (insulin lispro) is a rapid-acting analog of human insulin being developed by Sanofi. In 2016, Sanofi completed a Phase II comparison study of SAR322434 to Humalog (insulin lispro) in patients with T2DM also using insulin glargine (4).

GLP-1 Receptor Agonists

Intarcia Therapeutics is developing ITCA650 (exenatide) to provide patients with a convenient long-term treatment regimen. ITCA650 utilizes a small osmotic mini-pump that is placed sub-dermally to provide continuous and steady dosing of exenatide (6). In 2015, Intarcia initiated a Phase IIIb study to evaluate safety and tolerability of switching to one of two dosing strategies of ITCA 650 in patients with T2DM receiving stable doses of Liraglutide (4). Intarcia is aiming to file for regulatory approvals of ITCA650 during the first half of 2016 (6).

NN9535 (semaglutide) is a GLP-1 analog being developed by Novo Nordisk as an injectable weekly treatment for T2DM (4). Semaglutide makes use of Novo Nordisk’s protein-acylation technology. In 2016, Novo Nordisk released results from their SUSTAIN-5 Phase III trial. The trial was successful with semaglutide significantly improving blood sugar control compared to placebo when both were added to standard insulin therapy. Results from a final SUSTAIN trial are expected to be announced during the first half of 2016 (7).

Novo Nordisk is conducting Phase III development of NN9924 (semaglutide), a long-acting oral once daily semaglutide treatment for T2DM. In 2016, Novo Nordisk initiated a study of NN9924 versus Sitagliptin in patients with T2DM (4). If NN9924 ultimately reaches approval, it may become the first GLP-1 receptor agonist that can be taken orally.

Jiangsu Hengrui Medicine Co Ltd and Jiangsu Hansoh Pharmaceutical Co Ltd are developing PEX168 (pegylated loxenatide), a new GLP-1 analog for the treatment of T2DM, as an adjunctive therapy to metformin. Development is underway in China. In 2014, Jiangsu Hansoh Pharmaceutical initiated a Phase III trial of PEX168 in combination with metformin to evaluate safety and efficacy. The company also initiated a Phase IIIa study to evaluate the safety and efficacy of PEG168 monotherapy in patients with T2DM (4).

UNI-E4 (recombinant exenatide) is a GLP-1 receptor agonist being developed by Uni-Bio Science Ltd as a twice-daily injection for the treatment of T2DM. In 2015, Uni-Bio Science reported positive top-line results of a Phase III clinical trial which assessed the efficacy and safety of Uni-E4. Uni-Bio Science plans to submit a New Drug Application for UNI-E4 to the China Food and Drug Administration in 2016 (8).

Dipeptidyl Peptidase IV Inhibitor

SP2086 (retaglibtin) is a new dipeptidyl peptidase-4 (DPP-4) inhibitor being developed by Jiangsu Hengrui Medicine Co Ltd in China for the treatment of T2DM. As a DPP-4 inhibitor, the peptide increases circulating levels of glucagon-like peptide and glucose-dependent insulinotropic polypeptide resulting in stimulation of insulin secretion. In 2012, Jiangsu Hengrui Medicine initiated a Phase III study to assess the efficacy and safety of SP2086 monotherapy in T2DM patients. The company also initiated a Phase III study to assess the efficacy and safety of SP2086 in combination with Metformin (4).


The T2DM space is crowded but long-acting treatments and oral formulations offer the promise of new options to help physicians tailor treatments for patients based on their personal criteria. Efficacy and tolerability and cost may also vary among candidates in the pipeline offering additional advantages or disadvantages for patients. To support companies and organizations working in the area of diabetes, Bachem offers a wide array of catalog research peptides, custom peptide synthesis, production of peptide-based new chemical entities and generic active pharmaceuticals ingredients.



(1) U.S. Department of Health & Human Services. Accelerating Medicines Partnership: Type 2 Diabetes. National Institutes of Health. [Online] October 15, 2015. [Cited: March 29, 2016.]

(2) National Diabetes Statistics Report, 2014. Centers for Disease Control and Prevention. [Online] 2014. [Cited: March 29, 2016.]

(3) A, Garber. Diabetes Care. American Diabetes Association. [Online] May 2011. [Cited: April 4, 2016.]

(4) Medtrack. [Online] [Cited: March 28, 2016.]

(5) R, Krishnan. Biocon to conduct oral insulin trials on its own. Business Standard. [Online] January 27, 2016. [Cited: March 29, 2016.]

(6) ITCA 650. Intarcia Therapeutics. [Online] [Cited: March 29, 2016.]

(7) Novo Nordisk successfully completes fifth phase 3a trial with semaglutide in people with type 2 diabetes. Fierce Biotech. [Online] February 23, 2016. [Cited: March 29, 2016.]

(8) Uni-Bio Science Group Announces Positive Phase III Results for Uni-E4 in Type-2 Diabetes. Uni-Bio Science. [Online] August 3, 2015. [Cited: April 5, 2016.]


What is your official job title at Bachem?

Marketing Communications Associate.


How long have you been with Bachem?
I am with Bachem for almost 7 years now.


Briefly, what do you do at Bachem?

I am responsible for the planning and realization of tradeshows, conferences and events of the Bachem group. I also take care of the advertising material and gifts.


What is your academic background?

I made a commercial apprenticeship in the Pharma sector with higher vocational diploma. Afterwards, I completed a further education as a tourism- and event manager.


What do you like to do outside of work?

I enjoy reading books, listening to music and if time permits travelling within Switzerland and around the world.


What do you like most about your job?

My job allows me to be creative and to bring forward my own ideas. Furthermore, I am in daily contact with internal and external people which I really appreciate.


Thank you very much Stephanie.


Interesting news about peptides in basic research and pharmaceutical development:

Liraglutide may make high-fat foods less desirable to the brain’s reward centers– EurekAlert!

New procedure could improve success rate of cell transplant to cure type 1 diabetes– ScienceDaily

One-two punch: Small peptides attack ovarian cancer cells and their environment– Boston Children’s Hospital