Technology

XstalBio tackles challenging biologic formulation issues such as :

• API  can be too viscous at high concentration


• Required dosing too frequent


• Controlled release of API required (alter the PK profile)


• Unacceptable loss of high potency API at low concentrations


• Competitors hold blocking formulation patents


• Alternative delivery method favoured.


• Better adjuvant needed for target antigen(s)


• Cellular immune response required or duration of immunogenicity too short


• Elimination of cold-chain is desired


• CoG of product too high

 

Key Product EnablingTechnologies

 

High dosage delivery of proteins:

Stable solid-state formulations for reconstitution to very high aqueous concentrations

 

 

Key Characteristics for high dosage delivery: 

•  > 200 mg/ml for therapeutic mAbs

•  Rapid reconstitution at point of use  

•  FDA approved parenteral excipients

•  Osmolality applicable for subcutaneous administration

•  Viscosity allows delivery through 27 gauge needle

•  Extended shelf-life

 

Sustained-release of biologics:

Controlling API release over periods of days to weeks.

• Applicable to peptides, proteins, nucleic acids, polysaccharides etc

• Straightforward, high yield manufacturing process

• Administer using 27 gauge needle in WFI

• No polymers - release controlled by dissolution of calcium phosphate

• FDA approved parenteral excipients

• API unmodified and stabilised within particles

• Manufacturing is straightforward to apply and integrates into XstalBio's exisiting manufacturing process
  

 

Vaccines employing innovative adjuvants:

Co-delivery of antigen(s) and immunostimulant(s) to antigen presenting cells (APC).

• Applicable to acellular antigens, killed viruses, bacterial lysates, toxoids, plasmids

• Immobilisation on particles of size  and shape similar to bacterial pathogens

• Adaptive immune response  tailored by choice of TLR agonist

• Administer parenterally (27 G) or via alternate delivery routes

• Exclusively approved excipients with excellent tolerability

• Multivalent vaccines manufactured rapidly with straightforward QC

• Exceptional high and low temperature storage stability. No cold-chain requirement.

 

Cold-chain free biologic formulations:

Solid-state products stable on exposure to elevated temperature and humidity.

• Excellent retention of bioactivity with wide range of biomolecules

• > 40 client API successfully formulated

• Excellent resistance to stress with negligible protein aggregation or fragmentation

• mAb formulations stable for 1 year at 40^oC

• Free flowing dry powders of cytokines, hormones, plasmids, mAbs and mAb-derivatives

• Starting point for wide range of alternate delivery routes

 

Platform manufacturing process:  straightforward (semi-) continuous precipitation approach applicable to wide range of biologic products.

• Uses off-the-shelf components and low-footprint facilities

• GMP compatible process developed in collaboration with Boehringer Ingelheim Pharma using QbD approach

• Potential for very high throughput and lean manufacture

• Process highly differentiated  providing enhanced freedom to operate

• Can be integrated with existing fill-finish processes

 

 

Pulmonary Delivery of Biologics- systemic and topical.

XstalBio has developed it’s proprietary protein-coated microcrystal (PCMC®) technology to produce a respirable, stable pulmonary product   with  excellent powder handling characteristics.

 Broad applicability for a range of potency requirements

•  We can straightforwardly control the API payload of PCMC® for both high and low potency requirements

  

 Uniquely Placed: Particle engineering for advanced delivery  

 The XstalBio-PCMC® particles are uniquely placed to deliver two or more biological actives that are simultaneously immobilised in a chosen pre-set ratio on the surface of the particles, e.g. vaccine and adjuvant, e.g. CpG.   XstalBio’s particle engineering allows excellent delivery of multiple actives in a defined and predictable ratio. Importantly, control over particle size and shape is achieved by choosing the most appropriate processing conditions.

 

 

 

 

Manufacture: straightforward and robust

PCMC® for pulmonary delivery is straightforward to manufacture and has been scaled for production of clinical batches of product in collaboration with Boehringer Ingelheim Pharma KG.  XstalBio’s manufacturing process via third party diligence has been shown to be robust, straightforward, cost-effective and high yielding.

 

PCMC® for pulmonary delivery is available for licensing from XstalBio.

 

Client Programs  -  milestones delivered.

For third party clients, we have produced a range of pulmonary powders of   proprietary small proteins, mAbs and mAb fragments.

 A 6 month program with a XstalBio client achieved all of the following milestones:  

Formulation Characteristic Desired	Achieved
Particle sizes:  x 90 < 10 µm, x 50, 0.5µm–3µm	YES
Moisture Adsorption:   < 1 % over 0 -75 % R.H. T 25C	YES
No deliquescence below 90 % R.H. at 25 C	YES
Protein Stability: accelerated 3 month program, 40C, 75 % R.H.	YES
Sol aggregates < 5 %, no visible aggregates	YES
Solid-state form: high crystallinity, no tendency to form amorphous material	YES
Emitted Dose: > 80 % at 60 L/min	YES
Fine Particle Fraction (FPF):  > 50 %	YES
Particle stability: no change, following storage for a minimum 3 months	YES

Device performance with PCMC®

We recently collaborated with Aptar  coupling their  Prohaler device with XstalBio PCMC to assess pulmonary performance.  Delivering high payloads of API, FPFs of preliminary non-optimised test formulations delivered > 40 % FPF and emitted doses of > 96 % at low, 0.5 L inhalation volumes.

 

To find out more information on our Pulmonary Technology Offering, please contact us.